Variant allele predicted to encode a truncated non-functional protein.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.4689C>G (p.Tyr1563Ter)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Pathogenic
Apr 2016 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.4689C>G (p.Tyr1563Ter)
Variation ID: 37607 Accession: VCV000037607.95
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 17q21.31 17: 43071225 (GRCh38) [ NCBI UCSC ] 17: 41223242 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jun 28, 2015 Oct 20, 2024 Apr 22, 2016 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.4689C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Tyr1563Ter nonsense NM_001407571.1:c.4476C>G NP_001394500.1:p.Tyr1492Ter nonsense NM_001407581.1:c.4755C>G NP_001394510.1:p.Tyr1585Ter nonsense NM_001407582.1:c.4755C>G NP_001394511.1:p.Tyr1585Ter nonsense NM_001407583.1:c.4752C>G NP_001394512.1:p.Tyr1584Ter nonsense NM_001407585.1:c.4752C>G NP_001394514.1:p.Tyr1584Ter nonsense NM_001407587.1:c.4752C>G NP_001394516.1:p.Tyr1584Ter nonsense NM_001407590.1:c.4749C>G NP_001394519.1:p.Tyr1583Ter nonsense NM_001407591.1:c.4749C>G NP_001394520.1:p.Tyr1583Ter nonsense NM_001407593.1:c.4689C>G NP_001394522.1:p.Tyr1563Ter nonsense NM_001407594.1:c.4689C>G NP_001394523.1:p.Tyr1563Ter nonsense NM_001407596.1:c.4689C>G NP_001394525.1:p.Tyr1563Ter nonsense NM_001407597.1:c.4689C>G NP_001394526.1:p.Tyr1563Ter nonsense NM_001407598.1:c.4689C>G NP_001394527.1:p.Tyr1563Ter nonsense NM_001407602.1:c.4689C>G NP_001394531.1:p.Tyr1563Ter nonsense NM_001407603.1:c.4689C>G NP_001394532.1:p.Tyr1563Ter nonsense NM_001407605.1:c.4689C>G NP_001394534.1:p.Tyr1563Ter nonsense NM_001407610.1:c.4686C>G NP_001394539.1:p.Tyr1562Ter nonsense NM_001407611.1:c.4686C>G NP_001394540.1:p.Tyr1562Ter nonsense NM_001407612.1:c.4686C>G NP_001394541.1:p.Tyr1562Ter nonsense NM_001407613.1:c.4686C>G NP_001394542.1:p.Tyr1562Ter nonsense NM_001407614.1:c.4686C>G NP_001394543.1:p.Tyr1562Ter nonsense NM_001407615.1:c.4686C>G NP_001394544.1:p.Tyr1562Ter nonsense NM_001407616.1:c.4686C>G NP_001394545.1:p.Tyr1562Ter nonsense NM_001407617.1:c.4686C>G NP_001394546.1:p.Tyr1562Ter nonsense NM_001407618.1:c.4686C>G NP_001394547.1:p.Tyr1562Ter nonsense NM_001407619.1:c.4686C>G NP_001394548.1:p.Tyr1562Ter nonsense NM_001407620.1:c.4686C>G NP_001394549.1:p.Tyr1562Ter nonsense NM_001407621.1:c.4686C>G NP_001394550.1:p.Tyr1562Ter nonsense NM_001407622.1:c.4686C>G NP_001394551.1:p.Tyr1562Ter nonsense NM_001407623.1:c.4686C>G NP_001394552.1:p.Tyr1562Ter nonsense NM_001407624.1:c.4686C>G NP_001394553.1:p.Tyr1562Ter nonsense NM_001407625.1:c.4686C>G NP_001394554.1:p.Tyr1562Ter nonsense NM_001407626.1:c.4686C>G NP_001394555.1:p.Tyr1562Ter nonsense NM_001407627.1:c.4683C>G NP_001394556.1:p.Tyr1561Ter nonsense NM_001407628.1:c.4683C>G NP_001394557.1:p.Tyr1561Ter nonsense NM_001407629.1:c.4683C>G NP_001394558.1:p.Tyr1561Ter nonsense NM_001407630.1:c.4683C>G NP_001394559.1:p.Tyr1561Ter nonsense NM_001407631.1:c.4683C>G NP_001394560.1:p.Tyr1561Ter nonsense NM_001407632.1:c.4683C>G NP_001394561.1:p.Tyr1561Ter nonsense NM_001407633.1:c.4683C>G NP_001394562.1:p.Tyr1561Ter nonsense NM_001407634.1:c.4683C>G NP_001394563.1:p.Tyr1561Ter nonsense NM_001407635.1:c.4683C>G NP_001394564.1:p.Tyr1561Ter nonsense NM_001407636.1:c.4683C>G NP_001394565.1:p.Tyr1561Ter nonsense NM_001407637.1:c.4683C>G NP_001394566.1:p.Tyr1561Ter nonsense NM_001407638.1:c.4683C>G NP_001394567.1:p.Tyr1561Ter nonsense NM_001407639.1:c.4683C>G NP_001394568.1:p.Tyr1561Ter nonsense NM_001407640.1:c.4683C>G NP_001394569.1:p.Tyr1561Ter nonsense NM_001407641.1:c.4683C>G NP_001394570.1:p.Tyr1561Ter nonsense NM_001407642.1:c.4683C>G NP_001394571.1:p.Tyr1561Ter nonsense NM_001407644.1:c.4680C>G NP_001394573.1:p.Tyr1560Ter nonsense NM_001407645.1:c.4680C>G NP_001394574.1:p.Tyr1560Ter nonsense NM_001407646.1:c.4677C>G NP_001394575.1:p.Tyr1559Ter nonsense NM_001407647.1:c.4674C>G NP_001394576.1:p.Tyr1558Ter nonsense NM_001407648.1:c.4632C>G NP_001394577.1:p.Tyr1544Ter nonsense NM_001407649.1:c.4629C>G NP_001394578.1:p.Tyr1543Ter nonsense NM_001407652.1:c.4689C>G NP_001394581.1:p.Tyr1563Ter nonsense NM_001407653.1:c.4611C>G NP_001394582.1:p.Tyr1537Ter nonsense NM_001407654.1:c.4611C>G NP_001394583.1:p.Tyr1537Ter nonsense NM_001407655.1:c.4611C>G NP_001394584.1:p.Tyr1537Ter nonsense NM_001407656.1:c.4608C>G NP_001394585.1:p.Tyr1536Ter nonsense NM_001407657.1:c.4608C>G NP_001394586.1:p.Tyr1536Ter nonsense NM_001407658.1:c.4608C>G NP_001394587.1:p.Tyr1536Ter nonsense NM_001407659.1:c.4605C>G NP_001394588.1:p.Tyr1535Ter nonsense NM_001407660.1:c.4605C>G NP_001394589.1:p.Tyr1535Ter nonsense NM_001407661.1:c.4605C>G NP_001394590.1:p.Tyr1535Ter nonsense NM_001407662.1:c.4605C>G NP_001394591.1:p.Tyr1535Ter nonsense NM_001407663.1:c.4605C>G NP_001394592.1:p.Tyr1535Ter nonsense NM_001407664.1:c.4566C>G NP_001394593.1:p.Tyr1522Ter nonsense NM_001407665.1:c.4566C>G NP_001394594.1:p.Tyr1522Ter nonsense NM_001407666.1:c.4566C>G NP_001394595.1:p.Tyr1522Ter nonsense NM_001407667.1:c.4566C>G NP_001394596.1:p.Tyr1522Ter nonsense NM_001407668.1:c.4566C>G NP_001394597.1:p.Tyr1522Ter nonsense NM_001407669.1:c.4566C>G NP_001394598.1:p.Tyr1522Ter nonsense NM_001407670.1:c.4563C>G NP_001394599.1:p.Tyr1521Ter nonsense NM_001407671.1:c.4563C>G NP_001394600.1:p.Tyr1521Ter nonsense NM_001407672.1:c.4563C>G NP_001394601.1:p.Tyr1521Ter nonsense NM_001407673.1:c.4563C>G NP_001394602.1:p.Tyr1521Ter nonsense NM_001407674.1:c.4563C>G NP_001394603.1:p.Tyr1521Ter nonsense NM_001407675.1:c.4563C>G NP_001394604.1:p.Tyr1521Ter nonsense NM_001407676.1:c.4563C>G NP_001394605.1:p.Tyr1521Ter nonsense NM_001407677.1:c.4563C>G NP_001394606.1:p.Tyr1521Ter nonsense NM_001407678.1:c.4563C>G NP_001394607.1:p.Tyr1521Ter nonsense NM_001407679.1:c.4563C>G NP_001394608.1:p.Tyr1521Ter nonsense NM_001407680.1:c.4563C>G NP_001394609.1:p.Tyr1521Ter nonsense NM_001407681.1:c.4560C>G NP_001394610.1:p.Tyr1520Ter nonsense NM_001407682.1:c.4560C>G NP_001394611.1:p.Tyr1520Ter nonsense NM_001407683.1:c.4560C>G NP_001394612.1:p.Tyr1520Ter nonsense NM_001407684.1:c.4689C>G NP_001394613.1:p.Tyr1563Ter nonsense NM_001407685.1:c.4560C>G NP_001394614.1:p.Tyr1520Ter nonsense NM_001407686.1:c.4560C>G NP_001394615.1:p.Tyr1520Ter nonsense NM_001407687.1:c.4560C>G NP_001394616.1:p.Tyr1520Ter nonsense NM_001407688.1:c.4560C>G NP_001394617.1:p.Tyr1520Ter nonsense NM_001407689.1:c.4560C>G NP_001394618.1:p.Tyr1520Ter nonsense NM_001407690.1:c.4557C>G NP_001394619.1:p.Tyr1519Ter nonsense NM_001407691.1:c.4557C>G NP_001394620.1:p.Tyr1519Ter nonsense NM_001407692.1:c.4548C>G NP_001394621.1:p.Tyr1516Ter nonsense NM_001407694.1:c.4548C>G NP_001394623.1:p.Tyr1516Ter nonsense NM_001407695.1:c.4548C>G NP_001394624.1:p.Tyr1516Ter nonsense NM_001407696.1:c.4548C>G NP_001394625.1:p.Tyr1516Ter nonsense NM_001407697.1:c.4548C>G NP_001394626.1:p.Tyr1516Ter nonsense NM_001407698.1:c.4548C>G NP_001394627.1:p.Tyr1516Ter nonsense NM_001407724.1:c.4548C>G NP_001394653.1:p.Tyr1516Ter nonsense NM_001407725.1:c.4548C>G NP_001394654.1:p.Tyr1516Ter nonsense NM_001407726.1:c.4548C>G NP_001394655.1:p.Tyr1516Ter nonsense NM_001407727.1:c.4548C>G NP_001394656.1:p.Tyr1516Ter nonsense NM_001407728.1:c.4548C>G NP_001394657.1:p.Tyr1516Ter nonsense NM_001407729.1:c.4548C>G NP_001394658.1:p.Tyr1516Ter nonsense NM_001407730.1:c.4548C>G NP_001394659.1:p.Tyr1516Ter nonsense NM_001407731.1:c.4548C>G NP_001394660.1:p.Tyr1516Ter nonsense NM_001407732.1:c.4545C>G NP_001394661.1:p.Tyr1515Ter nonsense NM_001407733.1:c.4545C>G NP_001394662.1:p.Tyr1515Ter nonsense NM_001407734.1:c.4545C>G NP_001394663.1:p.Tyr1515Ter nonsense NM_001407735.1:c.4545C>G NP_001394664.1:p.Tyr1515Ter nonsense NM_001407736.1:c.4545C>G NP_001394665.1:p.Tyr1515Ter nonsense NM_001407737.1:c.4545C>G NP_001394666.1:p.Tyr1515Ter nonsense NM_001407738.1:c.4545C>G NP_001394667.1:p.Tyr1515Ter nonsense NM_001407739.1:c.4545C>G NP_001394668.1:p.Tyr1515Ter nonsense NM_001407740.1:c.4545C>G NP_001394669.1:p.Tyr1515Ter nonsense NM_001407741.1:c.4545C>G NP_001394670.1:p.Tyr1515Ter nonsense NM_001407742.1:c.4545C>G NP_001394671.1:p.Tyr1515Ter nonsense NM_001407743.1:c.4545C>G NP_001394672.1:p.Tyr1515Ter nonsense NM_001407744.1:c.4545C>G NP_001394673.1:p.Tyr1515Ter nonsense NM_001407745.1:c.4545C>G NP_001394674.1:p.Tyr1515Ter nonsense NM_001407746.1:c.4545C>G NP_001394675.1:p.Tyr1515Ter nonsense NM_001407747.1:c.4545C>G NP_001394676.1:p.Tyr1515Ter nonsense NM_001407748.1:c.4545C>G NP_001394677.1:p.Tyr1515Ter nonsense NM_001407749.1:c.4545C>G NP_001394678.1:p.Tyr1515Ter nonsense NM_001407750.1:c.4545C>G NP_001394679.1:p.Tyr1515Ter nonsense NM_001407751.1:c.4545C>G NP_001394680.1:p.Tyr1515Ter nonsense NM_001407752.1:c.4545C>G NP_001394681.1:p.Tyr1515Ter nonsense NM_001407838.1:c.4542C>G NP_001394767.1:p.Tyr1514Ter nonsense NM_001407839.1:c.4542C>G NP_001394768.1:p.Tyr1514Ter nonsense NM_001407841.1:c.4542C>G NP_001394770.1:p.Tyr1514Ter nonsense NM_001407842.1:c.4542C>G NP_001394771.1:p.Tyr1514Ter nonsense NM_001407843.1:c.4542C>G NP_001394772.1:p.Tyr1514Ter nonsense NM_001407844.1:c.4542C>G NP_001394773.1:p.Tyr1514Ter nonsense NM_001407845.1:c.4542C>G NP_001394774.1:p.Tyr1514Ter nonsense NM_001407846.1:c.4542C>G NP_001394775.1:p.Tyr1514Ter nonsense NM_001407847.1:c.4542C>G NP_001394776.1:p.Tyr1514Ter nonsense NM_001407848.1:c.4542C>G NP_001394777.1:p.Tyr1514Ter nonsense NM_001407849.1:c.4542C>G NP_001394778.1:p.Tyr1514Ter nonsense NM_001407850.1:c.4542C>G NP_001394779.1:p.Tyr1514Ter nonsense NM_001407851.1:c.4542C>G NP_001394780.1:p.Tyr1514Ter nonsense NM_001407852.1:c.4542C>G NP_001394781.1:p.Tyr1514Ter nonsense NM_001407853.1:c.4542C>G NP_001394782.1:p.Tyr1514Ter nonsense NM_001407854.1:c.4689C>G NP_001394783.1:p.Tyr1563Ter nonsense NM_001407858.1:c.4686C>G NP_001394787.1:p.Tyr1562Ter nonsense NM_001407859.1:c.4686C>G NP_001394788.1:p.Tyr1562Ter nonsense NM_001407860.1:c.4686C>G NP_001394789.1:p.Tyr1562Ter nonsense NM_001407861.1:c.4683C>G NP_001394790.1:p.Tyr1561Ter nonsense NM_001407862.1:c.4488C>G NP_001394791.1:p.Tyr1496Ter nonsense NM_001407863.1:c.4563C>G NP_001394792.1:p.Tyr1521Ter nonsense NM_001407874.1:c.4482C>G NP_001394803.1:p.Tyr1494Ter nonsense NM_001407875.1:c.4482C>G NP_001394804.1:p.Tyr1494Ter nonsense NM_001407879.1:c.4479C>G NP_001394808.1:p.Tyr1493Ter nonsense NM_001407881.1:c.4479C>G NP_001394810.1:p.Tyr1493Ter nonsense NM_001407882.1:c.4479C>G NP_001394811.1:p.Tyr1493Ter nonsense NM_001407884.1:c.4479C>G NP_001394813.1:p.Tyr1493Ter nonsense NM_001407885.1:c.4479C>G NP_001394814.1:p.Tyr1493Ter nonsense NM_001407886.1:c.4479C>G NP_001394815.1:p.Tyr1493Ter nonsense NM_001407887.1:c.4479C>G NP_001394816.1:p.Tyr1493Ter nonsense NM_001407889.1:c.4479C>G NP_001394818.1:p.Tyr1493Ter nonsense NM_001407894.1:c.4476C>G NP_001394823.1:p.Tyr1492Ter nonsense NM_001407895.1:c.4476C>G NP_001394824.1:p.Tyr1492Ter nonsense NM_001407896.1:c.4476C>G NP_001394825.1:p.Tyr1492Ter nonsense NM_001407897.1:c.4476C>G NP_001394826.1:p.Tyr1492Ter nonsense NM_001407898.1:c.4476C>G NP_001394827.1:p.Tyr1492Ter nonsense NM_001407899.1:c.4476C>G NP_001394828.1:p.Tyr1492Ter nonsense NM_001407900.1:c.4476C>G NP_001394829.1:p.Tyr1492Ter nonsense NM_001407902.1:c.4476C>G NP_001394831.1:p.Tyr1492Ter nonsense NM_001407904.1:c.4476C>G NP_001394833.1:p.Tyr1492Ter nonsense NM_001407906.1:c.4476C>G NP_001394835.1:p.Tyr1492Ter nonsense NM_001407907.1:c.4476C>G NP_001394836.1:p.Tyr1492Ter nonsense NM_001407908.1:c.4476C>G NP_001394837.1:p.Tyr1492Ter nonsense NM_001407909.1:c.4476C>G NP_001394838.1:p.Tyr1492Ter nonsense NM_001407910.1:c.4476C>G NP_001394839.1:p.Tyr1492Ter nonsense NM_001407915.1:c.4473C>G NP_001394844.1:p.Tyr1491Ter nonsense NM_001407916.1:c.4473C>G NP_001394845.1:p.Tyr1491Ter nonsense NM_001407917.1:c.4473C>G NP_001394846.1:p.Tyr1491Ter nonsense NM_001407918.1:c.4473C>G NP_001394847.1:p.Tyr1491Ter nonsense NM_001407919.1:c.4566C>G NP_001394848.1:p.Tyr1522Ter nonsense NM_001407920.1:c.4425C>G NP_001394849.1:p.Tyr1475Ter nonsense NM_001407921.1:c.4425C>G NP_001394850.1:p.Tyr1475Ter nonsense NM_001407922.1:c.4425C>G NP_001394851.1:p.Tyr1475Ter nonsense NM_001407923.1:c.4425C>G NP_001394852.1:p.Tyr1475Ter nonsense NM_001407924.1:c.4425C>G NP_001394853.1:p.Tyr1475Ter nonsense NM_001407925.1:c.4425C>G NP_001394854.1:p.Tyr1475Ter nonsense NM_001407926.1:c.4425C>G NP_001394855.1:p.Tyr1475Ter nonsense NM_001407927.1:c.4422C>G NP_001394856.1:p.Tyr1474Ter nonsense NM_001407928.1:c.4422C>G NP_001394857.1:p.Tyr1474Ter nonsense NM_001407929.1:c.4422C>G NP_001394858.1:p.Tyr1474Ter nonsense NM_001407930.1:c.4422C>G NP_001394859.1:p.Tyr1474Ter nonsense NM_001407931.1:c.4422C>G NP_001394860.1:p.Tyr1474Ter nonsense NM_001407932.1:c.4422C>G NP_001394861.1:p.Tyr1474Ter nonsense NM_001407933.1:c.4422C>G NP_001394862.1:p.Tyr1474Ter nonsense NM_001407934.1:c.4419C>G NP_001394863.1:p.Tyr1473Ter nonsense NM_001407935.1:c.4419C>G NP_001394864.1:p.Tyr1473Ter nonsense NM_001407936.1:c.4419C>G NP_001394865.1:p.Tyr1473Ter nonsense NM_001407937.1:c.4566C>G NP_001394866.1:p.Tyr1522Ter nonsense NM_001407938.1:c.4566C>G NP_001394867.1:p.Tyr1522Ter nonsense NM_001407939.1:c.4563C>G NP_001394868.1:p.Tyr1521Ter nonsense NM_001407940.1:c.4563C>G NP_001394869.1:p.Tyr1521Ter nonsense NM_001407941.1:c.4560C>G NP_001394870.1:p.Tyr1520Ter nonsense NM_001407942.1:c.4548C>G NP_001394871.1:p.Tyr1516Ter nonsense NM_001407943.1:c.4545C>G NP_001394872.1:p.Tyr1515Ter nonsense NM_001407944.1:c.4545C>G NP_001394873.1:p.Tyr1515Ter nonsense NM_001407945.1:c.4545C>G NP_001394874.1:p.Tyr1515Ter nonsense NM_001407946.1:c.4356C>G NP_001394875.1:p.Tyr1452Ter nonsense NM_001407947.1:c.4356C>G NP_001394876.1:p.Tyr1452Ter nonsense NM_001407948.1:c.4356C>G NP_001394877.1:p.Tyr1452Ter nonsense NM_001407949.1:c.4356C>G NP_001394878.1:p.Tyr1452Ter nonsense NM_001407950.1:c.4353C>G NP_001394879.1:p.Tyr1451Ter nonsense NM_001407951.1:c.4353C>G NP_001394880.1:p.Tyr1451Ter nonsense NM_001407952.1:c.4353C>G NP_001394881.1:p.Tyr1451Ter nonsense NM_001407953.1:c.4353C>G NP_001394882.1:p.Tyr1451Ter nonsense NM_001407954.1:c.4353C>G NP_001394883.1:p.Tyr1451Ter nonsense NM_001407955.1:c.4353C>G NP_001394884.1:p.Tyr1451Ter nonsense NM_001407956.1:c.4350C>G NP_001394885.1:p.Tyr1450Ter nonsense NM_001407957.1:c.4350C>G NP_001394886.1:p.Tyr1450Ter nonsense NM_001407958.1:c.4350C>G NP_001394887.1:p.Tyr1450Ter nonsense NM_001407959.1:c.4308C>G NP_001394888.1:p.Tyr1436Ter nonsense NM_001407960.1:c.4305C>G NP_001394889.1:p.Tyr1435Ter nonsense NM_001407962.1:c.4305C>G NP_001394891.1:p.Tyr1435Ter nonsense NM_001407963.1:c.4302C>G NP_001394892.1:p.Tyr1434Ter nonsense NM_001407964.1:c.4227C>G NP_001394893.1:p.Tyr1409Ter nonsense NM_001407965.1:c.4182C>G NP_001394894.1:p.Tyr1394Ter nonsense NM_001407966.1:c.3801C>G NP_001394895.1:p.Tyr1267Ter nonsense NM_001407967.1:c.3798C>G NP_001394896.1:p.Tyr1266Ter nonsense NM_001407968.1:c.2085C>G NP_001394897.1:p.Tyr695Ter nonsense NM_001407969.1:c.2082C>G NP_001394898.1:p.Tyr694Ter nonsense NM_001407970.1:c.1446C>G NP_001394899.1:p.Tyr482Ter nonsense NM_001407971.1:c.1446C>G NP_001394900.1:p.Tyr482Ter nonsense NM_001407972.1:c.1443C>G NP_001394901.1:p.Tyr481Ter nonsense NM_001407973.1:c.1380C>G NP_001394902.1:p.Tyr460Ter nonsense NM_001407974.1:c.1380C>G NP_001394903.1:p.Tyr460Ter nonsense NM_001407975.1:c.1380C>G NP_001394904.1:p.Tyr460Ter nonsense NM_001407976.1:c.1380C>G NP_001394905.1:p.Tyr460Ter nonsense NM_001407977.1:c.1380C>G NP_001394906.1:p.Tyr460Ter nonsense NM_001407978.1:c.1380C>G NP_001394907.1:p.Tyr460Ter nonsense NM_001407979.1:c.1377C>G NP_001394908.1:p.Tyr459Ter nonsense NM_001407980.1:c.1377C>G NP_001394909.1:p.Tyr459Ter nonsense NM_001407981.1:c.1377C>G NP_001394910.1:p.Tyr459Ter nonsense NM_001407982.1:c.1377C>G NP_001394911.1:p.Tyr459Ter nonsense NM_001407983.1:c.1377C>G NP_001394912.1:p.Tyr459Ter nonsense NM_001407984.1:c.1377C>G NP_001394913.1:p.Tyr459Ter nonsense NM_001407985.1:c.1377C>G NP_001394914.1:p.Tyr459Ter nonsense NM_001407986.1:c.1377C>G NP_001394915.1:p.Tyr459Ter nonsense NM_001407990.1:c.1377C>G NP_001394919.1:p.Tyr459Ter nonsense NM_001407991.1:c.1377C>G NP_001394920.1:p.Tyr459Ter nonsense NM_001407992.1:c.1377C>G NP_001394921.1:p.Tyr459Ter nonsense NM_001407993.1:c.1377C>G NP_001394922.1:p.Tyr459Ter nonsense NM_001408392.1:c.1374C>G NP_001395321.1:p.Tyr458Ter nonsense NM_001408396.1:c.1374C>G NP_001395325.1:p.Tyr458Ter nonsense NM_001408397.1:c.1374C>G NP_001395326.1:p.Tyr458Ter nonsense NM_001408398.1:c.1374C>G NP_001395327.1:p.Tyr458Ter nonsense NM_001408399.1:c.1374C>G NP_001395328.1:p.Tyr458Ter nonsense NM_001408400.1:c.1374C>G NP_001395329.1:p.Tyr458Ter nonsense NM_001408401.1:c.1374C>G NP_001395330.1:p.Tyr458Ter nonsense NM_001408402.1:c.1374C>G NP_001395331.1:p.Tyr458Ter nonsense NM_001408403.1:c.1374C>G NP_001395332.1:p.Tyr458Ter nonsense NM_001408404.1:c.1374C>G NP_001395333.1:p.Tyr458Ter nonsense NM_001408406.1:c.1371C>G NP_001395335.1:p.Tyr457Ter nonsense NM_001408407.1:c.1371C>G NP_001395336.1:p.Tyr457Ter nonsense NM_001408408.1:c.1371C>G NP_001395337.1:p.Tyr457Ter nonsense NM_001408409.1:c.1368C>G NP_001395338.1:p.Tyr456Ter nonsense NM_001408410.1:c.1305C>G NP_001395339.1:p.Tyr435Ter nonsense NM_001408411.1:c.1302C>G NP_001395340.1:p.Tyr434Ter nonsense NM_001408412.1:c.1299C>G NP_001395341.1:p.Tyr433Ter nonsense NM_001408413.1:c.1299C>G NP_001395342.1:p.Tyr433Ter nonsense NM_001408414.1:c.1299C>G NP_001395343.1:p.Tyr433Ter nonsense NM_001408415.1:c.1299C>G NP_001395344.1:p.Tyr433Ter nonsense NM_001408416.1:c.1299C>G NP_001395345.1:p.Tyr433Ter nonsense NM_001408418.1:c.1263C>G NP_001395347.1:p.Tyr421Ter nonsense NM_001408419.1:c.1263C>G NP_001395348.1:p.Tyr421Ter nonsense NM_001408420.1:c.1263C>G NP_001395349.1:p.Tyr421Ter nonsense NM_001408421.1:c.1260C>G NP_001395350.1:p.Tyr420Ter nonsense NM_001408422.1:c.1260C>G NP_001395351.1:p.Tyr420Ter nonsense NM_001408423.1:c.1260C>G NP_001395352.1:p.Tyr420Ter nonsense NM_001408424.1:c.1260C>G NP_001395353.1:p.Tyr420Ter nonsense NM_001408425.1:c.1257C>G NP_001395354.1:p.Tyr419Ter nonsense NM_001408426.1:c.1257C>G NP_001395355.1:p.Tyr419Ter nonsense NM_001408427.1:c.1257C>G NP_001395356.1:p.Tyr419Ter nonsense NM_001408428.1:c.1257C>G NP_001395357.1:p.Tyr419Ter nonsense NM_001408429.1:c.1257C>G NP_001395358.1:p.Tyr419Ter nonsense NM_001408430.1:c.1257C>G NP_001395359.1:p.Tyr419Ter nonsense NM_001408431.1:c.1257C>G NP_001395360.1:p.Tyr419Ter nonsense NM_001408432.1:c.1254C>G NP_001395361.1:p.Tyr418Ter nonsense NM_001408433.1:c.1254C>G NP_001395362.1:p.Tyr418Ter nonsense NM_001408434.1:c.1254C>G NP_001395363.1:p.Tyr418Ter nonsense NM_001408435.1:c.1254C>G NP_001395364.1:p.Tyr418Ter nonsense NM_001408436.1:c.1254C>G NP_001395365.1:p.Tyr418Ter nonsense NM_001408437.1:c.1254C>G NP_001395366.1:p.Tyr418Ter nonsense NM_001408438.1:c.1254C>G NP_001395367.1:p.Tyr418Ter nonsense NM_001408439.1:c.1254C>G NP_001395368.1:p.Tyr418Ter nonsense NM_001408440.1:c.1254C>G NP_001395369.1:p.Tyr418Ter nonsense NM_001408441.1:c.1254C>G NP_001395370.1:p.Tyr418Ter nonsense NM_001408442.1:c.1254C>G NP_001395371.1:p.Tyr418Ter nonsense NM_001408443.1:c.1254C>G NP_001395372.1:p.Tyr418Ter nonsense NM_001408444.1:c.1254C>G NP_001395373.1:p.Tyr418Ter nonsense NM_001408445.1:c.1251C>G NP_001395374.1:p.Tyr417Ter nonsense NM_001408446.1:c.1251C>G NP_001395375.1:p.Tyr417Ter nonsense NM_001408447.1:c.1251C>G NP_001395376.1:p.Tyr417Ter nonsense NM_001408448.1:c.1251C>G NP_001395377.1:p.Tyr417Ter nonsense NM_001408450.1:c.1251C>G NP_001395379.1:p.Tyr417Ter nonsense NM_001408451.1:c.1245C>G NP_001395380.1:p.Tyr415Ter nonsense NM_001408452.1:c.1239C>G NP_001395381.1:p.Tyr413Ter nonsense NM_001408453.1:c.1239C>G NP_001395382.1:p.Tyr413Ter nonsense NM_001408454.1:c.1239C>G NP_001395383.1:p.Tyr413Ter nonsense NM_001408455.1:c.1239C>G NP_001395384.1:p.Tyr413Ter nonsense NM_001408456.1:c.1239C>G NP_001395385.1:p.Tyr413Ter nonsense NM_001408457.1:c.1239C>G NP_001395386.1:p.Tyr413Ter nonsense NM_001408458.1:c.1236C>G NP_001395387.1:p.Tyr412Ter nonsense NM_001408459.1:c.1236C>G NP_001395388.1:p.Tyr412Ter nonsense NM_001408460.1:c.1236C>G NP_001395389.1:p.Tyr412Ter nonsense NM_001408461.1:c.1236C>G NP_001395390.1:p.Tyr412Ter nonsense NM_001408462.1:c.1236C>G NP_001395391.1:p.Tyr412Ter nonsense NM_001408463.1:c.1236C>G NP_001395392.1:p.Tyr412Ter nonsense NM_001408464.1:c.1236C>G NP_001395393.1:p.Tyr412Ter nonsense NM_001408465.1:c.1236C>G NP_001395394.1:p.Tyr412Ter nonsense NM_001408466.1:c.1236C>G NP_001395395.1:p.Tyr412Ter nonsense NM_001408467.1:c.1236C>G NP_001395396.1:p.Tyr412Ter nonsense NM_001408468.1:c.1233C>G NP_001395397.1:p.Tyr411Ter nonsense NM_001408469.1:c.1233C>G NP_001395398.1:p.Tyr411Ter nonsense NM_001408470.1:c.1233C>G NP_001395399.1:p.Tyr411Ter nonsense NM_001408472.1:c.1377C>G NP_001395401.1:p.Tyr459Ter nonsense NM_001408473.1:c.1374C>G NP_001395402.1:p.Tyr458Ter nonsense NM_001408474.1:c.1179C>G NP_001395403.1:p.Tyr393Ter nonsense NM_001408475.1:c.1176C>G NP_001395404.1:p.Tyr392Ter nonsense NM_001408476.1:c.1176C>G NP_001395405.1:p.Tyr392Ter nonsense NM_001408478.1:c.1170C>G NP_001395407.1:p.Tyr390Ter nonsense NM_001408479.1:c.1170C>G NP_001395408.1:p.Tyr390Ter nonsense NM_001408480.1:c.1170C>G NP_001395409.1:p.Tyr390Ter nonsense NM_001408481.1:c.1167C>G NP_001395410.1:p.Tyr389Ter nonsense NM_001408482.1:c.1167C>G NP_001395411.1:p.Tyr389Ter nonsense NM_001408483.1:c.1167C>G NP_001395412.1:p.Tyr389Ter nonsense NM_001408484.1:c.1167C>G NP_001395413.1:p.Tyr389Ter nonsense NM_001408485.1:c.1167C>G NP_001395414.1:p.Tyr389Ter nonsense NM_001408489.1:c.1167C>G NP_001395418.1:p.Tyr389Ter nonsense NM_001408490.1:c.1167C>G NP_001395419.1:p.Tyr389Ter nonsense NM_001408491.1:c.1167C>G NP_001395420.1:p.Tyr389Ter nonsense NM_001408492.1:c.1164C>G NP_001395421.1:p.Tyr388Ter nonsense NM_001408493.1:c.1164C>G NP_001395422.1:p.Tyr388Ter nonsense NM_001408494.1:c.1140C>G NP_001395423.1:p.Tyr380Ter nonsense NM_001408495.1:c.1134C>G NP_001395424.1:p.Tyr378Ter nonsense NM_001408496.1:c.1116C>G NP_001395425.1:p.Tyr372Ter nonsense NM_001408497.1:c.1116C>G NP_001395426.1:p.Tyr372Ter nonsense NM_001408498.1:c.1116C>G NP_001395427.1:p.Tyr372Ter nonsense NM_001408499.1:c.1116C>G NP_001395428.1:p.Tyr372Ter nonsense NM_001408500.1:c.1116C>G NP_001395429.1:p.Tyr372Ter nonsense NM_001408501.1:c.1116C>G NP_001395430.1:p.Tyr372Ter nonsense NM_001408502.1:c.1113C>G NP_001395431.1:p.Tyr371Ter nonsense NM_001408503.1:c.1113C>G NP_001395432.1:p.Tyr371Ter nonsense NM_001408504.1:c.1113C>G NP_001395433.1:p.Tyr371Ter nonsense NM_001408505.1:c.1110C>G NP_001395434.1:p.Tyr370Ter nonsense NM_001408506.1:c.1053C>G NP_001395435.1:p.Tyr351Ter nonsense NM_001408507.1:c.1050C>G NP_001395436.1:p.Tyr350Ter nonsense NM_001408508.1:c.1041C>G NP_001395437.1:p.Tyr347Ter nonsense NM_001408509.1:c.1038C>G NP_001395438.1:p.Tyr346Ter nonsense NM_001408510.1:c.999C>G NP_001395439.1:p.Tyr333Ter nonsense NM_001408511.1:c.996C>G NP_001395440.1:p.Tyr332Ter nonsense NM_001408512.1:c.876C>G NP_001395441.1:p.Tyr292Ter nonsense NM_001408513.1:c.849C>G NP_001395442.1:p.Tyr283Ter nonsense NM_007297.4:c.4548C>G NP_009228.2:p.Tyr1516Ter nonsense NM_007298.4:c.1377C>G NP_009229.2:p.Tyr459Ter nonsense NM_007299.4:c.1377C>G NP_009230.2:p.Tyr459Ter nonsense NM_007300.4:c.4752C>G NP_009231.2:p.Tyr1584Ter nonsense NM_007304.2:c.1377C>G NP_009235.2:p.Tyr459Ter nonsense NR_027676.2:n.4866C>G non-coding transcript variant NC_000017.11:g.43071225G>C NC_000017.10:g.41223242G>C NG_005905.2:g.146759C>G LRG_292:g.146759C>G LRG_292t1:c.4689C>G LRG_292p1:p.Tyr1563Ter U14680.1:n.4808C>G - Protein change
- Y1563*, Y1584*, Y1516*, Y459*, Y1267*, Y1434*, Y1450*, Y1451*, Y1514*, Y1519*, Y1537*, Y1543*, Y1559*, Y1583*, Y333*, Y388*, Y389*, Y390*, Y392*, Y411*, Y415*, Y460*, Y283*, Y292*, Y346*, Y351*, Y371*, Y418*, Y420*, Y421*, Y482*, Y1266*, Y1394*, Y1409*, Y1436*, Y1492*, Y1493*, Y1515*, Y1522*, Y1536*, Y1544*, Y1585*, Y332*, Y347*, Y370*, Y372*, Y380*, Y393*, Y433*, Y434*, Y456*, Y458*, Y694*, Y1474*, Y1475*, Y1494*, Y1520*, Y1535*, Y1558*, Y1560*, Y1562*, Y1435*, Y1452*, Y1473*, Y1491*, Y1496*, Y1521*, Y1561*, Y350*, Y378*, Y412*, Y413*, Y417*, Y419*, Y435*, Y457*, Y481*, Y695*
- Other names
-
p.Y1563*:TAC>TAG
4808C>G
- Canonical SPDI
- NC_000017.11:43071224:G:C
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD) 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00000
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
| BRCA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
13041 | 14847 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (19) |
reviewed by expert panel
|
Apr 22, 2016 | RCV000031188.38 | |
| Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
|
Jan 15, 2024 | RCV000048631.31 | |
| Pathogenic (14) |
criteria provided, multiple submitters, no conflicts
|
Jan 1, 2024 | RCV000159994.58 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 28, 2023 | RCV000131835.20 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Feb 23, 2017 | RCV000464295.9 | |
| Pathogenic (1) |
no assertion criteria provided
|
Dec 1, 2018 | RCV000785416.10 | |
|
BRCA1-related disorder
|
Pathogenic (1) |
criteria provided, single submitter
|
Oct 3, 2023 | RCV004554629.1 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Apr 22, 2016)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV000282332.1
First in ClinVar: Jun 24, 2016 Last updated: Jun 24, 2016 |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
|
|
|
Pathogenic
(Jun 06, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine
Accession: SCV000839898.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
The c.4689C>G (p.Tyr1563*) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 8554067, 23110154]. This variant creates … (more)
The c.4689C>G (p.Tyr1563*) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 8554067, 23110154]. This variant creates a premature stop codon at amino acid position 1563 of the BRCA1 protein. This variant is thus predicted to result in a loss of function of the protein. This variant has not been observed in the ExAC population database. This variant is thus classified as pathogenic. (less)
|
|
|
Pathogenic
(Oct 21, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
MGZ Medical Genetics Center
Accession: SCV002580873.1
First in ClinVar: Oct 15, 2022 Last updated: Oct 15, 2022
Comment:
ACMG criteria applied: PVS1, PM2_SUP, PP1
|
Number of individuals with the variant: 1
Sex: male
|
|
|
Pathogenic
(Nov 30, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000210185.14
First in ClinVar: Feb 24, 2015 Last updated: Dec 31, 2022 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Serova 1996, Shih 2002, Turkovic 2010, Schneegans 2012, Wong-Brown 2015, Nguyen-Dumont 2018); Not observed at a significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 4808C>G; This variant is associated with the following publications: (PMID: 27167707, 30128899, 29422015, 30551077, 34657373, 29922827, 30040829, 28888541, 11844822, 8554067, 22160602, 23110154, 25556971, 24830819, 25682074, 26843898, 25948282, 25085752, 29339979, 28324225, 29907814, 29446198, 30487145, 30216591, 30322717, 20807450, 32072338, 30787465, 30612635, 29625052, 31447099, 35596902, 36367610, 36171877) (less)
|
|
|
Pathogenic
(Feb 23, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Baylor Genetics
Accession: SCV000540932.1
First in ClinVar: Apr 17, 2017 Last updated: Apr 17, 2017 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Jul 01, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Medical Genetics, Oslo University Hospital
Accession: SCV000564327.1
First in ClinVar: Nov 05, 2016 Last updated: Nov 05, 2016 |
Number of individuals with the variant: 5
|
|
|
Pathogenic
(Sep 21, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744610.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Pathogenic
(Jan 02, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Genetics and Molecular Pathology, SA Pathology
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV002761615.1
First in ClinVar: Dec 17, 2022 Last updated: Dec 17, 2022 |
|
|
|
Pathogenic
(Nov 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002009436.3
First in ClinVar: Oct 30, 2021 Last updated: Jul 16, 2023 |
|
|
|
Pathogenic
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002550967.4
First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023 |
|
|
|
Pathogenic
(Jun 27, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
maternal
|
Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV001440857.5
First in ClinVar: Oct 31, 2020 Last updated: Aug 23, 2023 |
Comment:
Criteria applied: PVS1,PS4,PM2_SUP
Clinical Features:
Family history of cancer (present)
Sex: female
|
|
|
Pathogenic
(Aug 24, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004215019.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
|
Pathogenic
(Apr 18, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002024610.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(Jan 15, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000076644.15
First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Tyr1563*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Tyr1563*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357433, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 8554067, 20727672, 23110154, 25066507, 27167707). It has also been observed to segregate with disease in related individuals. This variant is also known as 4808C>G. ClinVar contains an entry for this variant (Variation ID: 37607). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Mar 21, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001157089.2
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
Comment:
The BRCA1 c.4689C>G; p.Tyr1563Ter variant (rs80357433), also known as 4808C>G, is reported in the literature in multiple individuals and families affected with hereditary breast and … (more)
The BRCA1 c.4689C>G; p.Tyr1563Ter variant (rs80357433), also known as 4808C>G, is reported in the literature in multiple individuals and families affected with hereditary breast and ovarian cancer (Pern 2012, Rebbeck 2018, Schneegans 2012, Serova 1996). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Pern F et al. Mutation analysis of BRCA1, BRCA2, PALB2 and BRD7 in a hospital-based series of German patients with triple-negative breast cancer. PLoS One. 2012;7(10):e47993. Rebbeck TR et al. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. Hum Mutat. 2018 May;39(5):593-620. Schneegans SM Validation of three BRCA1/2 mutation-carrier probability models Myriad, BRCAPRO and BOADICEA in a population-based series of 183 German families. Fam Cancer. 2012 Jun;11(2):181-8. Serova O et al. A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families. Am J Hum Genet. 1996 Jan;58(1):42-51. (less)
|
|
|
Pathogenic
(Jan 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001747802.20
First in ClinVar: Jul 10, 2021 Last updated: Oct 20, 2024 |
Comment:
BRCA1: PVS1, PM2, PS4:Moderate
Number of individuals with the variant: 4
|
|
|
Pathogenic
(Apr 21, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Michigan Medical Genetics Laboratories, University of Michigan
Accession: SCV000267714.1
First in ClinVar: May 06, 2016 Last updated: May 06, 2016 |
Tissue: Blood
|
|
|
Pathogenic
(May 16, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
{Breast-ovarian cancer, familial, 1}
Affected status: yes
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000593676.1
First in ClinVar: Nov 05, 2016 Last updated: Nov 05, 2016 |
|
|
|
Pathogenic
(Jul 28, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743389.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Pathogenic
(Jan 01, 2017)
|
criteria provided, single submitter
Method: research
|
Breast-ovarian cancer, familial 1
Affected status: unknown
Allele origin:
germline
|
Snyder Lab, Genetics Department, Stanford University
Accession: SCV000853089.1
First in ClinVar: Nov 25, 2018 Last updated: Nov 25, 2018 |
|
|
|
Pathogenic
(May 14, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000226313.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 3
Sex: mixed
|
|
|
Pathogenic
(Jan 01, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
GeneKor MSA
Accession: SCV000693540.2
First in ClinVar: Jan 07, 2017 Last updated: May 04, 2020 |
Comment:
This sequence change creates a premature translational stop signal at codon 1563 (p.Tyr1563*). It is expected to result in an absent or disrupted protein product. … (more)
This sequence change creates a premature translational stop signal at codon 1563 (p.Tyr1563*). It is expected to result in an absent or disrupted protein product. Truncating variants in BRCA1 are known to be pathogenic. This particular truncation has been reported in the literature in individuals affected with hereditary breast and ovarian cancer (PMID: 8554067, 23110154, 25066507, 20727672, 27167707). This sequence change is also known as 4808C>G in the literature. This particular variant has been described in the mutation database ClinVar (Variation ID: 37607) as pathogenic. (less)
|
|
|
Pathogenic
(Jul 23, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast and ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699164.2
First in ClinVar: Dec 26, 2017 Last updated: Aug 10, 2020 |
Comment:
Variant summary: BRCA1 c.4689C>G (p.Tyr1563X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Variant summary: BRCA1 c.4689C>G (p.Tyr1563X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 250704 control chromosomes (gnomAD). c.4689C>G has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (Alsop_2012, Bergman_2005, Couch_2015, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 21 ClinVar submitters, including one expert panel (ENIGMA), (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
|
|
|
Pathogenic
(Feb 22, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics and Genomics, Karolinska University Hospital
Accession: SCV001450206.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Sep 15, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001905671.1
First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
Clinical Features:
Breast carcinoma (present)
Sex: female
|
|
|
Pathogenic
(Oct 02, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge
Accession: SCV000326033.4
First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022 |
|
|
|
Pathogenic
(Apr 28, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000488572.2
First in ClinVar: Nov 05, 2016 Last updated: Dec 24, 2022 |
|
|
|
Pathogenic
(Oct 03, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
BRCA1-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000806958.2
First in ClinVar: Sep 13, 2018 Last updated: Nov 20, 2023 |
Comment:
The BRCA1 c.4689C>G variant is predicted to result in premature protein termination (p.Tyr1563*). This variant has previously been reported to be causative for hereditary breast … (more)
The BRCA1 c.4689C>G variant is predicted to result in premature protein termination (p.Tyr1563*). This variant has previously been reported to be causative for hereditary breast and ovarian cancer (Serova et al. 1996. PubMed ID: 8554067; Pern et al. 2012. PubMed ID: 23110154). This variant has also been recorded as a breast cancer associated variant within the Breast Cancer Information Core (BIC) database (http://research.nhgri.nih.gov/projects/bic/) and as pathogenic in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/37607/). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-41223242-G-C). Nonsense variants in BRCA1 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
|
|
|
Pathogenic
(Aug 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000888922.4
First in ClinVar: Mar 13, 2019 Last updated: Jan 06, 2024 |
Comment:
This variant causes the premature termination of BRCA1 protein synthesis. In the published literature, this variant has been reported in individuals with breast and/or ovarian … (more)
This variant causes the premature termination of BRCA1 protein synthesis. In the published literature, this variant has been reported in individuals with breast and/or ovarian cancer (PMIDs: 29907814 (2018), 28324225 (2017), 8554067 (1996)). The frequency of this variant in the general population, 0.0000088 (1/113148 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic. (less)
|
|
|
Pathogenic
(Nov 23, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not provided
Affected status: unknown
Allele origin:
germline
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV001715198.2
First in ClinVar: Jun 15, 2021 Last updated: Jan 26, 2024 |
Comment:
PP5, PM2, PS4_moderate, PVS1
Number of individuals with the variant: 4
|
|
|
Pathogenic
(Feb 28, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000683206.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This variant changes 1 nucleotide in exon 15 of the BRCA1 gene, creating a premature translation stop signal. RNA analyses have shown that this variant … (more)
This variant changes 1 nucleotide in exon 15 of the BRCA1 gene, creating a premature translation stop signal. RNA analyses have shown that this variant leads to an absence of RNA transcript and protein product (PMID: 8554067, 12393792). This variant has been detected in multiple individuals and families affected with breast and ovarian cancer (PMID: 8554067, 11844822, 15951958, 20727672, 20807450, 22160602, 22711857, 22762150, 23110154, 25066507, 25452441, 27167707, 29339979, 33471991). This variant has been identified in 1/250704 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
|
|
|
Pathogenic
(Jan 22, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004817640.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Comment:
This variant changes 1 nucleotide in exon 15 of the BRCA1 gene, creating a premature translation stop signal. RNA analyses have shown that this variant … (more)
This variant changes 1 nucleotide in exon 15 of the BRCA1 gene, creating a premature translation stop signal. RNA analyses have shown that this variant leads to an absence of RNA transcript and protein product (PMID: 8554067, 12393792). This variant has been detected in multiple individuals and families affected with breast and ovarian cancer (PMID: 8554067, 11844822, 15951958, 20727672, 20807450, 22160602, 22711857, 22762150, 23110154, 25066507, 25452441, 27167707, 29339979, 33471991). This variant has been identified in 1/250704 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
Number of individuals with the variant: 3
|
|
|
Pathogenic
(Aug 05, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004847950.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
The p.Tyr1563X variant in BRCA1 has been reported in >50 individuals with BRCA1-associated cancers (Breast cancer information core (BIC) database, Serova 1996, Pern 2012, Janavičius … (more)
The p.Tyr1563X variant in BRCA1 has been reported in >50 individuals with BRCA1-associated cancers (Breast cancer information core (BIC) database, Serova 1996, Pern 2012, Janavičius 2014, Koczkowska 2016) and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1563, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism in hereditary breast and ovarian cancer (HBOC). Additionally, the p.Tyr1563X variant was classified as Pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA Expert Panel (SCV000282332.1). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner based upon its predicted impact to the protein, absence from controls, and numerous reports in affected individuals. (less)
|
|
|
Pathogenic
(Nov 29, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000186890.8
First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024 |
Comment:
The p.Y1563* pathogenic mutation (also known as c.4689C>G), located in coding exon 14 of the BRCA1 gene, results from a C to G substitution at … (more)
The p.Y1563* pathogenic mutation (also known as c.4689C>G), located in coding exon 14 of the BRCA1 gene, results from a C to G substitution at nucleotide position 4689. This changes the amino acid from a tyrosine to a stop codon within coding exon 14. This mutation has been detected in multiple hereditary breast and ovarian cancer (HBOC) syndrome families (Serova O et al. Am. J. Hum. Genet. 1996 Jan;58:42-51; Iyevleva AG et al. Cancer Lett. 2010 Dec;298:258-63; Schneegans S et al. Fam. Cancer. 2012 Jun;11:181-8; Lecarpentier J et al. Breast Cancer Res. 2012 Jul;14:R99; Pern F et al. PLoS One. 2012;7:e47993; Rebbeck TR et al. Hum. Mutat., 2018 May;39:593-620), and a history weighing algorithm classified it as pathogenic (Pruss D et al. Breast Cancer Res. Treat., 2014 Aug;147:119-32). One study demonstrated that this mutation triggers nonsense mediated decay (NMD) and results in less than half the amount of BRCA1 mRNA compared to wild-type (Perrin-Vidoz L et al. Hum. Mol. Genet. 2002 Nov;11:2805-14). Of note, this alteration is also designated as 4808C>G in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
|
|
|
Pathogenic
(Jul 05, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics Laboratory, Skane University Hospital Lund
Accession: SCV005199712.1
First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733607.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
|
|
|
Pathogenic
(Aug 26, 2022)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
BRCAlab, Lund University
Accession: SCV002588816.1
First in ClinVar: Apr 01, 2023 Last updated: Apr 01, 2023 |
|
|
|
Pathogenic
(May 29, 2002)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline,
unknown
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145160.2
First in ClinVar: Apr 01, 2014 Last updated: Jun 28, 2015 |
Observation 1:
Number of individuals with the variant: 19
Observation 2:
Number of individuals with the variant: 1
Geographic origin: Germany
Observation 3:
Number of individuals with the variant: 4
Geographic origin: Western European
Observation 4:
Number of individuals with the variant: 3
Ethnicity/Population group: Caucasian
Geographic origin: English, Germany, Ireland
Observation 5:
Number of individuals with the variant: 4
Ethnicity/Population group: Central/Eastern European
Observation 6:
Number of individuals with the variant: 1
Ethnicity/Population group: Czech, German
Observation 7:
Number of individuals with the variant: 1
Ethnicity/Population group: Czech, Polish
Observation 8:
Number of individuals with the variant: 1
Ethnicity/Population group: Scottish, German
Observation 9:
Number of individuals with the variant: 13
Ethnicity/Population group: Western European
Observation 10:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, English, Scottish, German
Observation 11:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, German
Observation 12:
Number of individuals with the variant: 1
Ethnicity/Population group: Western Europeanan, Central/Eastern European
Observation 13:
Number of individuals with the variant: 1
Ethnicity/Population group: Western, Central/Eastern European
Observation 14:
Number of individuals with the variant: 1
Observation 15:
Number of individuals with the variant: 2
Geographic origin: Germany
|
|
|
Pathogenic
(Mar 04, 2013)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000053788.6
First in ClinVar: Apr 04, 2013 Last updated: Jun 24, 2016 |
|
|
|
Pathogenic
(Jan 31, 2014)
|
no assertion criteria provided
Method: research
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000587421.1 First in ClinVar: Aug 05, 2017 Last updated: Aug 05, 2017 |
|
|
|
Pathogenic
(Dec 01, 2018)
|
no assertion criteria provided
Method: research
|
Ovarian neoplasm
Affected status: yes
Allele origin:
germline
|
German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
Accession: SCV000923988.1
First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019 |
|
|
|
Uncertain significance
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591537.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Number of individuals with the variant: 1
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
The c.4689C>G (p.Tyr1563*) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 8554067, 23110154]. This variant creates a premature stop codon at amino acid position 1563 of the BRCA1 protein. This variant is thus predicted to result in a loss of function of the protein. This variant has not been observed in the ExAC population database. This variant is thus classified as pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Serova 1996, Shih 2002, Turkovic 2010, Schneegans 2012, Wong-Brown 2015, Nguyen-Dumont 2018); Not observed at a significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 4808C>G; This variant is associated with the following publications: (PMID: 27167707, 30128899, 29422015, 30551077, 34657373, 29922827, 30040829, 28888541, 11844822, 8554067, 22160602, 23110154, 25556971, 24830819, 25682074, 26843898, 25948282, 25085752, 29339979, 28324225, 29907814, 29446198, 30487145, 30216591, 30322717, 20807450, 32072338, 30787465, 30612635, 29625052, 31447099, 35596902, 36367610, 36171877)
Comment:
Criteria applied: PVS1,PS4,PM2_SUP
Comment:
This sequence change creates a premature translational stop signal (p.Tyr1563*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357433, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 8554067, 20727672, 23110154, 25066507, 27167707). It has also been observed to segregate with disease in related individuals. This variant is also known as 4808C>G. ClinVar contains an entry for this variant (Variation ID: 37607). For these reasons, this variant has been classified as Pathogenic.
Comment:
The BRCA1 c.4689C>G; p.Tyr1563Ter variant (rs80357433), also known as 4808C>G, is reported in the literature in multiple individuals and families affected with hereditary breast and ovarian cancer (Pern 2012, Rebbeck 2018, Schneegans 2012, Serova 1996). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Pern F et al. Mutation analysis of BRCA1, BRCA2, PALB2 and BRD7 in a hospital-based series of German patients with triple-negative breast cancer. PLoS One. 2012;7(10):e47993. Rebbeck TR et al. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. Hum Mutat. 2018 May;39(5):593-620. Schneegans SM Validation of three BRCA1/2 mutation-carrier probability models Myriad, BRCAPRO and BOADICEA in a population-based series of 183 German families. Fam Cancer. 2012 Jun;11(2):181-8. Serova O et al. A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families. Am J Hum Genet. 1996 Jan;58(1):42-51.
Comment:
BRCA1: PVS1, PM2, PS4:Moderate
Comment:
This sequence change creates a premature translational stop signal at codon 1563 (p.Tyr1563*). It is expected to result in an absent or disrupted protein product. Truncating variants in BRCA1 are known to be pathogenic. This particular truncation has been reported in the literature in individuals affected with hereditary breast and ovarian cancer (PMID: 8554067, 23110154, 25066507, 20727672, 27167707). This sequence change is also known as 4808C>G in the literature. This particular variant has been described in the mutation database ClinVar (Variation ID: 37607) as pathogenic.
Comment:
Variant summary: BRCA1 c.4689C>G (p.Tyr1563X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 250704 control chromosomes (gnomAD). c.4689C>G has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (Alsop_2012, Bergman_2005, Couch_2015, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 21 ClinVar submitters, including one expert panel (ENIGMA), (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
The BRCA1 c.4689C>G variant is predicted to result in premature protein termination (p.Tyr1563*). This variant has previously been reported to be causative for hereditary breast and ovarian cancer (Serova et al. 1996. PubMed ID: 8554067; Pern et al. 2012. PubMed ID: 23110154). This variant has also been recorded as a breast cancer associated variant within the Breast Cancer Information Core (BIC) database (http://research.nhgri.nih.gov/projects/bic/) and as pathogenic in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/37607/). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-41223242-G-C). Nonsense variants in BRCA1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Comment:
This variant causes the premature termination of BRCA1 protein synthesis. In the published literature, this variant has been reported in individuals with breast and/or ovarian cancer (PMIDs: 29907814 (2018), 28324225 (2017), 8554067 (1996)). The frequency of this variant in the general population, 0.0000088 (1/113148 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic.
Comment:
PP5, PM2, PS4_moderate, PVS1
Comment:
This variant changes 1 nucleotide in exon 15 of the BRCA1 gene, creating a premature translation stop signal. RNA analyses have shown that this variant leads to an absence of RNA transcript and protein product (PMID: 8554067, 12393792). This variant has been detected in multiple individuals and families affected with breast and ovarian cancer (PMID: 8554067, 11844822, 15951958, 20727672, 20807450, 22160602, 22711857, 22762150, 23110154, 25066507, 25452441, 27167707, 29339979, 33471991). This variant has been identified in 1/250704 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
This variant changes 1 nucleotide in exon 15 of the BRCA1 gene, creating a premature translation stop signal. RNA analyses have shown that this variant leads to an absence of RNA transcript and protein product (PMID: 8554067, 12393792). This variant has been detected in multiple individuals and families affected with breast and ovarian cancer (PMID: 8554067, 11844822, 15951958, 20727672, 20807450, 22160602, 22711857, 22762150, 23110154, 25066507, 25452441, 27167707, 29339979, 33471991). This variant has been identified in 1/250704 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
The p.Tyr1563X variant in BRCA1 has been reported in >50 individuals with BRCA1-associated cancers (Breast cancer information core (BIC) database, Serova 1996, Pern 2012, Janavičius 2014, Koczkowska 2016) and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1563, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism in hereditary breast and ovarian cancer (HBOC). Additionally, the p.Tyr1563X variant was classified as Pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA Expert Panel (SCV000282332.1). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner based upon its predicted impact to the protein, absence from controls, and numerous reports in affected individuals.
Comment:
The p.Y1563* pathogenic mutation (also known as c.4689C>G), located in coding exon 14 of the BRCA1 gene, results from a C to G substitution at nucleotide position 4689. This changes the amino acid from a tyrosine to a stop codon within coding exon 14. This mutation has been detected in multiple hereditary breast and ovarian cancer (HBOC) syndrome families (Serova O et al. Am. J. Hum. Genet. 1996 Jan;58:42-51; Iyevleva AG et al. Cancer Lett. 2010 Dec;298:258-63; Schneegans S et al. Fam. Cancer. 2012 Jun;11:181-8; Lecarpentier J et al. Breast Cancer Res. 2012 Jul;14:R99; Pern F et al. PLoS One. 2012;7:e47993; Rebbeck TR et al. Hum. Mutat., 2018 May;39:593-620), and a history weighing algorithm classified it as pathogenic (Pruss D et al. Breast Cancer Res. Treat., 2014 Aug;147:119-32). One study demonstrated that this mutation triggers nonsense mediated decay (NMD) and results in less than half the amount of BRCA1 mRNA compared to wild-type (Perrin-Vidoz L et al. Hum. Mol. Genet. 2002 Nov;11:2805-14). Of note, this alteration is also designated as 4808C>G in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
Variant allele predicted to encode a truncated non-functional protein.
Comment:
The c.4689C>G (p.Tyr1563*) variant in the BRCA1 gene has been detected multiple patients with breast cancer and/or ovarian cancer [PMID 8554067, 23110154]. This variant creates a premature stop codon at amino acid position 1563 of the BRCA1 protein. This variant is thus predicted to result in a loss of function of the protein. This variant has not been observed in the ExAC population database. This variant is thus classified as pathogenic.
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Serova 1996, Shih 2002, Turkovic 2010, Schneegans 2012, Wong-Brown 2015, Nguyen-Dumont 2018); Not observed at a significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 4808C>G; This variant is associated with the following publications: (PMID: 27167707, 30128899, 29422015, 30551077, 34657373, 29922827, 30040829, 28888541, 11844822, 8554067, 22160602, 23110154, 25556971, 24830819, 25682074, 26843898, 25948282, 25085752, 29339979, 28324225, 29907814, 29446198, 30487145, 30216591, 30322717, 20807450, 32072338, 30787465, 30612635, 29625052, 31447099, 35596902, 36367610, 36171877)
Comment:
Criteria applied: PVS1,PS4,PM2_SUP
Comment:
This sequence change creates a premature translational stop signal (p.Tyr1563*) in the BRCA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80357433, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with hereditary breast and ovarian cancer (PMID: 8554067, 20727672, 23110154, 25066507, 27167707). It has also been observed to segregate with disease in related individuals. This variant is also known as 4808C>G. ClinVar contains an entry for this variant (Variation ID: 37607). For these reasons, this variant has been classified as Pathogenic.
Comment:
The BRCA1 c.4689C>G; p.Tyr1563Ter variant (rs80357433), also known as 4808C>G, is reported in the literature in multiple individuals and families affected with hereditary breast and ovarian cancer (Pern 2012, Rebbeck 2018, Schneegans 2012, Serova 1996). This variant is only observed on one allele in the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Pern F et al. Mutation analysis of BRCA1, BRCA2, PALB2 and BRD7 in a hospital-based series of German patients with triple-negative breast cancer. PLoS One. 2012;7(10):e47993. Rebbeck TR et al. Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. Hum Mutat. 2018 May;39(5):593-620. Schneegans SM Validation of three BRCA1/2 mutation-carrier probability models Myriad, BRCAPRO and BOADICEA in a population-based series of 183 German families. Fam Cancer. 2012 Jun;11(2):181-8. Serova O et al. A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families. Am J Hum Genet. 1996 Jan;58(1):42-51.
Comment:
BRCA1: PVS1, PM2, PS4:Moderate
Comment:
This sequence change creates a premature translational stop signal at codon 1563 (p.Tyr1563*). It is expected to result in an absent or disrupted protein product. Truncating variants in BRCA1 are known to be pathogenic. This particular truncation has been reported in the literature in individuals affected with hereditary breast and ovarian cancer (PMID: 8554067, 23110154, 25066507, 20727672, 27167707). This sequence change is also known as 4808C>G in the literature. This particular variant has been described in the mutation database ClinVar (Variation ID: 37607) as pathogenic.
Comment:
Variant summary: BRCA1 c.4689C>G (p.Tyr1563X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 250704 control chromosomes (gnomAD). c.4689C>G has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (Alsop_2012, Bergman_2005, Couch_2015, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. 21 ClinVar submitters, including one expert panel (ENIGMA), (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
The BRCA1 c.4689C>G variant is predicted to result in premature protein termination (p.Tyr1563*). This variant has previously been reported to be causative for hereditary breast and ovarian cancer (Serova et al. 1996. PubMed ID: 8554067; Pern et al. 2012. PubMed ID: 23110154). This variant has also been recorded as a breast cancer associated variant within the Breast Cancer Information Core (BIC) database (http://research.nhgri.nih.gov/projects/bic/) and as pathogenic in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/37607/). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-41223242-G-C). Nonsense variants in BRCA1 are expected to be pathogenic. This variant is interpreted as pathogenic.
Comment:
This variant causes the premature termination of BRCA1 protein synthesis. In the published literature, this variant has been reported in individuals with breast and/or ovarian cancer (PMIDs: 29907814 (2018), 28324225 (2017), 8554067 (1996)). The frequency of this variant in the general population, 0.0000088 (1/113148 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is consistent with pathogenicity. Based on the available information, this variant is classified as pathogenic.
Comment:
PP5, PM2, PS4_moderate, PVS1
Comment:
This variant changes 1 nucleotide in exon 15 of the BRCA1 gene, creating a premature translation stop signal. RNA analyses have shown that this variant leads to an absence of RNA transcript and protein product (PMID: 8554067, 12393792). This variant has been detected in multiple individuals and families affected with breast and ovarian cancer (PMID: 8554067, 11844822, 15951958, 20727672, 20807450, 22160602, 22711857, 22762150, 23110154, 25066507, 25452441, 27167707, 29339979, 33471991). This variant has been identified in 1/250704 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
This variant changes 1 nucleotide in exon 15 of the BRCA1 gene, creating a premature translation stop signal. RNA analyses have shown that this variant leads to an absence of RNA transcript and protein product (PMID: 8554067, 12393792). This variant has been detected in multiple individuals and families affected with breast and ovarian cancer (PMID: 8554067, 11844822, 15951958, 20727672, 20807450, 22160602, 22711857, 22762150, 23110154, 25066507, 25452441, 27167707, 29339979, 33471991). This variant has been identified in 1/250704 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Comment:
The p.Tyr1563X variant in BRCA1 has been reported in >50 individuals with BRCA1-associated cancers (Breast cancer information core (BIC) database, Serova 1996, Pern 2012, Janavičius 2014, Koczkowska 2016) and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1563, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established disease mechanism in hereditary breast and ovarian cancer (HBOC). Additionally, the p.Tyr1563X variant was classified as Pathogenic on April 22, 2016 by the ClinGen-approved ENIGMA Expert Panel (SCV000282332.1). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner based upon its predicted impact to the protein, absence from controls, and numerous reports in affected individuals.
Comment:
The p.Y1563* pathogenic mutation (also known as c.4689C>G), located in coding exon 14 of the BRCA1 gene, results from a C to G substitution at nucleotide position 4689. This changes the amino acid from a tyrosine to a stop codon within coding exon 14. This mutation has been detected in multiple hereditary breast and ovarian cancer (HBOC) syndrome families (Serova O et al. Am. J. Hum. Genet. 1996 Jan;58:42-51; Iyevleva AG et al. Cancer Lett. 2010 Dec;298:258-63; Schneegans S et al. Fam. Cancer. 2012 Jun;11:181-8; Lecarpentier J et al. Breast Cancer Res. 2012 Jul;14:R99; Pern F et al. PLoS One. 2012;7:e47993; Rebbeck TR et al. Hum. Mutat., 2018 May;39:593-620), and a history weighing algorithm classified it as pathogenic (Pruss D et al. Breast Cancer Res. Treat., 2014 Aug;147:119-32). One study demonstrated that this mutation triggers nonsense mediated decay (NMD) and results in less than half the amount of BRCA1 mRNA compared to wild-type (Perrin-Vidoz L et al. Hum. Mol. Genet. 2002 Nov;11:2805-14). Of note, this alteration is also designated as 4808C>G in published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
| High-frequency actionable pathogenic exome variants in an average-risk cohort. | Rego S | Cold Spring Harbor molecular case studies | 2018 | PMID: 30487145 |
| The germline mutational landscape of BRCA1 and BRCA2 in Brazil. | Palmero EI | Scientific reports | 2018 | PMID: 29907814 |
| Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. | Rebbeck TR | Human mutation | 2018 | PMID: 29446198 |
| BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large cancer genetics clinic in Norway. | Heramb C | Hereditary cancer in clinical practice | 2018 | PMID: 29339979 |
| Spectrum of genetic variants of BRCA1 and BRCA2 in a German single center study. | Meisel C | Archives of gynecology and obstetrics | 2017 | PMID: 28324225 |
| Detection of somatic BRCA1/2 mutations in ovarian cancer - next-generation sequencing analysis of 100 cases. | Koczkowska M | Cancer medicine | 2016 | PMID: 27167707 |
| Recurrent mutations of BRCA1, BRCA2 and PALB2 in the population of breast and ovarian cancer patients in Southern Poland. | Wojcik P | Hereditary cancer in clinical practice | 2016 | PMID: 26843898 |
| Development and Validation of a Next-Generation Sequencing Assay for BRCA1 and BRCA2 Variants for the Clinical Laboratory. | Strom CM | PloS one | 2015 | PMID: 26295337 |
| Inherited mutations in 17 breast cancer susceptibility genes among a large triple-negative breast cancer cohort unselected for family history of breast cancer. | Couch FJ | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2015 | PMID: 25452441 |
| Development and validation of a new algorithm for the reclassification of genetic variants identified in the BRCA1 and BRCA2 genes. | Pruss D | Breast cancer research and treatment | 2014 | PMID: 25085752 |
| Comprehensive BRCA1 and BRCA2 mutational profile in Lithuania. | Janavičius R | Cancer genetics | 2014 | PMID: 25066507 |
| The validation and clinical implementation of BRCAplus: a comprehensive high-risk breast cancer diagnostic assay. | Chong HK | PloS one | 2014 | PMID: 24830819 |
| Mutation analysis of BRCA1, BRCA2, PALB2 and BRD7 in a hospital-based series of German patients with triple-negative breast cancer. | Pern F | PloS one | 2012 | PMID: 23110154 |
| Variation in breast cancer risk associated with factors related to pregnancies according to truncating mutation location, in the French National BRCA1 and BRCA2 mutations carrier cohort (GENEPSO). | Lecarpentier J | Breast cancer research : BCR | 2012 | PMID: 22762150 |
| BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. | Alsop K | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2012 | PMID: 22711857 |
| Validation of three BRCA1/2 mutation-carrier probability models Myriad, BRCAPRO and BOADICEA in a population-based series of 183 German families. | Schneegans SM | Familial cancer | 2012 | PMID: 22160602 |
| Comparing the frequency of common genetic variants and haplotypes between carriers and non-carriers of BRCA1 and BRCA2 deleterious mutations in Australian women diagnosed with breast cancer before 40 years of age. | Turkovic L | BMC cancer | 2010 | PMID: 20807450 |
| Non-founder BRCA1 mutations in Russian breast cancer patients. | Iyevleva AG | Cancer letters | 2010 | PMID: 20727672 |
| Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. | Borg A | Human mutation | 2010 | PMID: 20104584 |
| Caspase-dependent BRCA1 cleavage facilitates chemotherapy-induced apoptosis. | Dizin E | Apoptosis : an international journal on programmed cell death | 2008 | PMID: 18071904 |
| A high frequency of germline BRCA1/2 mutations in western Sweden detected with complementary screening techniques. | Bergman A | Familial cancer | 2005 | PMID: 15951958 |
| The nonsense-mediated mRNA decay pathway triggers degradation of most BRCA1 mRNAs bearing premature termination codons. | Perrin-Vidoz L | Human molecular genetics | 2002 | PMID: 12393792 |
| BRCA1 and BRCA2 mutation frequency in women evaluated in a breast cancer risk evaluation clinic. | Shih HA | Journal of clinical oncology : official journal of the American Society of Clinical Oncology | 2002 | PMID: 11844822 |
| The histologic phenotypes of breast carcinoma occurring before age 40 years in women with and without BRCA1 or BRCA2 germline mutations: a population-based study. | Armes JE | Cancer | 1998 | PMID: 9840533 |
| A high incidence of BRCA1 mutations in 20 breast-ovarian cancer families. | Serova O | American journal of human genetics | 1996 | PMID: 8554067 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA1 | - | - | - | - |
| click to load more click to collapse | ||||
Text-mined citations for rs80357433 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 03, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.