ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5254G>C (p.Ala1752Pro)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.5254G>C (p.Ala1752Pro)
Variation ID: 55483 Accession: VCV000055483.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43057075 (GRCh38) [ NCBI UCSC ] 17: 41209092 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Apr 1, 2014 May 1, 2024 Dec 14, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.5254G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ala1752Pro missense NM_001407571.1:c.5041G>C NP_001394500.1:p.Ala1681Pro missense NM_001407581.1:c.5320G>C NP_001394510.1:p.Ala1774Pro missense NM_001407582.1:c.5320G>C NP_001394511.1:p.Ala1774Pro missense NM_001407583.1:c.5317G>C NP_001394512.1:p.Ala1773Pro missense NM_001407585.1:c.5317G>C NP_001394514.1:p.Ala1773Pro missense NM_001407587.1:c.5317G>C NP_001394516.1:p.Ala1773Pro missense NM_001407590.1:c.5314G>C NP_001394519.1:p.Ala1772Pro missense NM_001407591.1:c.5314G>C NP_001394520.1:p.Ala1772Pro missense NM_001407593.1:c.5254G>C NP_001394522.1:p.Ala1752Pro missense NM_001407594.1:c.5254G>C NP_001394523.1:p.Ala1752Pro missense NM_001407596.1:c.5254G>C NP_001394525.1:p.Ala1752Pro missense NM_001407597.1:c.5254G>C NP_001394526.1:p.Ala1752Pro missense NM_001407598.1:c.5254G>C NP_001394527.1:p.Ala1752Pro missense NM_001407602.1:c.5254G>C NP_001394531.1:p.Ala1752Pro missense NM_001407603.1:c.5254G>C NP_001394532.1:p.Ala1752Pro missense NM_001407605.1:c.5254G>C NP_001394534.1:p.Ala1752Pro missense NM_001407610.1:c.5251G>C NP_001394539.1:p.Ala1751Pro missense NM_001407611.1:c.5251G>C NP_001394540.1:p.Ala1751Pro missense NM_001407612.1:c.5251G>C NP_001394541.1:p.Ala1751Pro missense NM_001407613.1:c.5251G>C NP_001394542.1:p.Ala1751Pro missense NM_001407614.1:c.5251G>C NP_001394543.1:p.Ala1751Pro missense NM_001407615.1:c.5251G>C NP_001394544.1:p.Ala1751Pro missense NM_001407616.1:c.5251G>C NP_001394545.1:p.Ala1751Pro missense NM_001407617.1:c.5251G>C NP_001394546.1:p.Ala1751Pro missense NM_001407618.1:c.5251G>C NP_001394547.1:p.Ala1751Pro missense NM_001407619.1:c.5251G>C NP_001394548.1:p.Ala1751Pro missense NM_001407620.1:c.5251G>C NP_001394549.1:p.Ala1751Pro missense NM_001407621.1:c.5251G>C NP_001394550.1:p.Ala1751Pro missense NM_001407622.1:c.5251G>C NP_001394551.1:p.Ala1751Pro missense NM_001407623.1:c.5251G>C NP_001394552.1:p.Ala1751Pro missense NM_001407624.1:c.5251G>C NP_001394553.1:p.Ala1751Pro missense NM_001407625.1:c.5251G>C NP_001394554.1:p.Ala1751Pro missense NM_001407626.1:c.5251G>C NP_001394555.1:p.Ala1751Pro missense NM_001407627.1:c.5248G>C NP_001394556.1:p.Ala1750Pro missense NM_001407628.1:c.5248G>C NP_001394557.1:p.Ala1750Pro missense NM_001407629.1:c.5248G>C NP_001394558.1:p.Ala1750Pro missense NM_001407630.1:c.5248G>C NP_001394559.1:p.Ala1750Pro missense NM_001407631.1:c.5248G>C NP_001394560.1:p.Ala1750Pro missense NM_001407632.1:c.5248G>C NP_001394561.1:p.Ala1750Pro missense NM_001407633.1:c.5248G>C NP_001394562.1:p.Ala1750Pro missense NM_001407634.1:c.5248G>C NP_001394563.1:p.Ala1750Pro missense NM_001407635.1:c.5248G>C NP_001394564.1:p.Ala1750Pro missense NM_001407636.1:c.5248G>C NP_001394565.1:p.Ala1750Pro missense NM_001407637.1:c.5248G>C NP_001394566.1:p.Ala1750Pro missense NM_001407638.1:c.5248G>C NP_001394567.1:p.Ala1750Pro missense NM_001407639.1:c.5248G>C NP_001394568.1:p.Ala1750Pro missense NM_001407640.1:c.5248G>C NP_001394569.1:p.Ala1750Pro missense NM_001407641.1:c.5248G>C NP_001394570.1:p.Ala1750Pro missense NM_001407642.1:c.5248G>C NP_001394571.1:p.Ala1750Pro missense NM_001407644.1:c.5245G>C NP_001394573.1:p.Ala1749Pro missense NM_001407645.1:c.5245G>C NP_001394574.1:p.Ala1749Pro missense NM_001407646.1:c.5242G>C NP_001394575.1:p.Ala1748Pro missense NM_001407647.1:c.5239G>C NP_001394576.1:p.Ala1747Pro missense NM_001407648.1:c.5197G>C NP_001394577.1:p.Ala1733Pro missense NM_001407649.1:c.5194G>C NP_001394578.1:p.Ala1732Pro missense NM_001407652.1:c.5176G>C NP_001394581.1:p.Ala1726Pro missense NM_001407653.1:c.5176G>C NP_001394582.1:p.Ala1726Pro missense NM_001407654.1:c.5176G>C NP_001394583.1:p.Ala1726Pro missense NM_001407655.1:c.5176G>C NP_001394584.1:p.Ala1726Pro missense NM_001407656.1:c.5173G>C NP_001394585.1:p.Ala1725Pro missense NM_001407657.1:c.5173G>C NP_001394586.1:p.Ala1725Pro missense NM_001407658.1:c.5173G>C NP_001394587.1:p.Ala1725Pro missense NM_001407659.1:c.5170G>C NP_001394588.1:p.Ala1724Pro missense NM_001407660.1:c.5170G>C NP_001394589.1:p.Ala1724Pro missense NM_001407661.1:c.5170G>C NP_001394590.1:p.Ala1724Pro missense NM_001407662.1:c.5170G>C NP_001394591.1:p.Ala1724Pro missense NM_001407663.1:c.5170G>C NP_001394592.1:p.Ala1724Pro missense NM_001407664.1:c.5131G>C NP_001394593.1:p.Ala1711Pro missense NM_001407665.1:c.5131G>C NP_001394594.1:p.Ala1711Pro missense NM_001407666.1:c.5131G>C NP_001394595.1:p.Ala1711Pro missense NM_001407667.1:c.5131G>C NP_001394596.1:p.Ala1711Pro missense NM_001407668.1:c.5131G>C NP_001394597.1:p.Ala1711Pro missense NM_001407669.1:c.5131G>C NP_001394598.1:p.Ala1711Pro missense NM_001407670.1:c.5128G>C NP_001394599.1:p.Ala1710Pro missense NM_001407671.1:c.5128G>C NP_001394600.1:p.Ala1710Pro missense NM_001407672.1:c.5128G>C NP_001394601.1:p.Ala1710Pro missense NM_001407673.1:c.5128G>C NP_001394602.1:p.Ala1710Pro missense NM_001407674.1:c.5128G>C NP_001394603.1:p.Ala1710Pro missense NM_001407675.1:c.5128G>C NP_001394604.1:p.Ala1710Pro missense NM_001407676.1:c.5128G>C NP_001394605.1:p.Ala1710Pro missense NM_001407677.1:c.5128G>C NP_001394606.1:p.Ala1710Pro missense NM_001407678.1:c.5128G>C NP_001394607.1:p.Ala1710Pro missense NM_001407679.1:c.5128G>C NP_001394608.1:p.Ala1710Pro missense NM_001407680.1:c.5128G>C NP_001394609.1:p.Ala1710Pro missense NM_001407681.1:c.5125G>C NP_001394610.1:p.Ala1709Pro missense NM_001407682.1:c.5125G>C NP_001394611.1:p.Ala1709Pro missense NM_001407683.1:c.5125G>C NP_001394612.1:p.Ala1709Pro missense NM_001407684.1:c.5254G>C NP_001394613.1:p.Ala1752Pro missense NM_001407685.1:c.5125G>C NP_001394614.1:p.Ala1709Pro missense NM_001407686.1:c.5125G>C NP_001394615.1:p.Ala1709Pro missense NM_001407687.1:c.5125G>C NP_001394616.1:p.Ala1709Pro missense NM_001407688.1:c.5125G>C NP_001394617.1:p.Ala1709Pro missense NM_001407689.1:c.5125G>C NP_001394618.1:p.Ala1709Pro missense NM_001407690.1:c.5122G>C NP_001394619.1:p.Ala1708Pro missense NM_001407691.1:c.5122G>C NP_001394620.1:p.Ala1708Pro missense NM_001407692.1:c.5113G>C NP_001394621.1:p.Ala1705Pro missense NM_001407694.1:c.5113G>C NP_001394623.1:p.Ala1705Pro missense NM_001407695.1:c.5113G>C NP_001394624.1:p.Ala1705Pro missense NM_001407696.1:c.5113G>C NP_001394625.1:p.Ala1705Pro missense NM_001407697.1:c.5113G>C NP_001394626.1:p.Ala1705Pro missense NM_001407698.1:c.5113G>C NP_001394627.1:p.Ala1705Pro missense NM_001407724.1:c.5113G>C NP_001394653.1:p.Ala1705Pro missense NM_001407725.1:c.5113G>C NP_001394654.1:p.Ala1705Pro missense NM_001407726.1:c.5113G>C NP_001394655.1:p.Ala1705Pro missense NM_001407727.1:c.5113G>C NP_001394656.1:p.Ala1705Pro missense NM_001407728.1:c.5113G>C NP_001394657.1:p.Ala1705Pro missense NM_001407729.1:c.5113G>C NP_001394658.1:p.Ala1705Pro missense NM_001407730.1:c.5113G>C NP_001394659.1:p.Ala1705Pro missense NM_001407731.1:c.5113G>C NP_001394660.1:p.Ala1705Pro missense NM_001407732.1:c.5110G>C NP_001394661.1:p.Ala1704Pro missense NM_001407733.1:c.5110G>C NP_001394662.1:p.Ala1704Pro missense NM_001407734.1:c.5110G>C NP_001394663.1:p.Ala1704Pro missense NM_001407735.1:c.5110G>C NP_001394664.1:p.Ala1704Pro missense NM_001407736.1:c.5110G>C NP_001394665.1:p.Ala1704Pro missense NM_001407737.1:c.5110G>C NP_001394666.1:p.Ala1704Pro missense NM_001407738.1:c.5110G>C NP_001394667.1:p.Ala1704Pro missense NM_001407739.1:c.5110G>C NP_001394668.1:p.Ala1704Pro missense NM_001407740.1:c.5110G>C NP_001394669.1:p.Ala1704Pro missense NM_001407741.1:c.5110G>C NP_001394670.1:p.Ala1704Pro missense NM_001407742.1:c.5110G>C NP_001394671.1:p.Ala1704Pro missense NM_001407743.1:c.5110G>C NP_001394672.1:p.Ala1704Pro missense NM_001407744.1:c.5110G>C NP_001394673.1:p.Ala1704Pro missense NM_001407745.1:c.5110G>C NP_001394674.1:p.Ala1704Pro missense NM_001407746.1:c.5110G>C NP_001394675.1:p.Ala1704Pro missense NM_001407747.1:c.5110G>C NP_001394676.1:p.Ala1704Pro missense NM_001407748.1:c.5110G>C NP_001394677.1:p.Ala1704Pro missense NM_001407749.1:c.5110G>C NP_001394678.1:p.Ala1704Pro missense NM_001407750.1:c.5110G>C NP_001394679.1:p.Ala1704Pro missense NM_001407751.1:c.5110G>C NP_001394680.1:p.Ala1704Pro missense NM_001407752.1:c.5110G>C NP_001394681.1:p.Ala1704Pro missense NM_001407838.1:c.5107G>C NP_001394767.1:p.Ala1703Pro missense NM_001407839.1:c.5107G>C NP_001394768.1:p.Ala1703Pro missense NM_001407841.1:c.5107G>C NP_001394770.1:p.Ala1703Pro missense NM_001407842.1:c.5107G>C NP_001394771.1:p.Ala1703Pro missense NM_001407843.1:c.5107G>C NP_001394772.1:p.Ala1703Pro missense NM_001407844.1:c.5107G>C NP_001394773.1:p.Ala1703Pro missense NM_001407845.1:c.5107G>C NP_001394774.1:p.Ala1703Pro missense NM_001407846.1:c.5107G>C NP_001394775.1:p.Ala1703Pro missense NM_001407847.1:c.5107G>C NP_001394776.1:p.Ala1703Pro missense NM_001407848.1:c.5107G>C NP_001394777.1:p.Ala1703Pro missense NM_001407849.1:c.5107G>C NP_001394778.1:p.Ala1703Pro missense NM_001407850.1:c.5107G>C NP_001394779.1:p.Ala1703Pro missense NM_001407851.1:c.5107G>C NP_001394780.1:p.Ala1703Pro missense NM_001407852.1:c.5107G>C NP_001394781.1:p.Ala1703Pro missense NM_001407853.1:c.5107G>C NP_001394782.1:p.Ala1703Pro missense NM_001407854.1:c.5254G>C NP_001394783.1:p.Ala1752Pro missense NM_001407858.1:c.5251G>C NP_001394787.1:p.Ala1751Pro missense NM_001407859.1:c.5251G>C NP_001394788.1:p.Ala1751Pro missense NM_001407860.1:c.5251G>C NP_001394789.1:p.Ala1751Pro missense NM_001407861.1:c.5248G>C NP_001394790.1:p.Ala1750Pro missense NM_001407862.1:c.5053G>C NP_001394791.1:p.Ala1685Pro missense NM_001407863.1:c.5050G>C NP_001394792.1:p.Ala1684Pro missense NM_001407874.1:c.5047G>C NP_001394803.1:p.Ala1683Pro missense NM_001407875.1:c.5047G>C NP_001394804.1:p.Ala1683Pro missense NM_001407879.1:c.5044G>C NP_001394808.1:p.Ala1682Pro missense NM_001407881.1:c.5044G>C NP_001394810.1:p.Ala1682Pro missense NM_001407882.1:c.5044G>C NP_001394811.1:p.Ala1682Pro missense NM_001407884.1:c.5044G>C NP_001394813.1:p.Ala1682Pro missense NM_001407885.1:c.5044G>C NP_001394814.1:p.Ala1682Pro missense NM_001407886.1:c.5044G>C NP_001394815.1:p.Ala1682Pro missense NM_001407887.1:c.5044G>C NP_001394816.1:p.Ala1682Pro missense NM_001407889.1:c.5044G>C NP_001394818.1:p.Ala1682Pro missense NM_001407894.1:c.5041G>C NP_001394823.1:p.Ala1681Pro missense NM_001407895.1:c.5041G>C NP_001394824.1:p.Ala1681Pro missense NM_001407896.1:c.5041G>C NP_001394825.1:p.Ala1681Pro missense NM_001407897.1:c.5041G>C NP_001394826.1:p.Ala1681Pro missense NM_001407898.1:c.5041G>C NP_001394827.1:p.Ala1681Pro missense NM_001407899.1:c.5041G>C NP_001394828.1:p.Ala1681Pro missense NM_001407900.1:c.5041G>C NP_001394829.1:p.Ala1681Pro missense NM_001407902.1:c.5041G>C NP_001394831.1:p.Ala1681Pro missense NM_001407904.1:c.5041G>C NP_001394833.1:p.Ala1681Pro missense NM_001407906.1:c.5041G>C NP_001394835.1:p.Ala1681Pro missense NM_001407907.1:c.5041G>C NP_001394836.1:p.Ala1681Pro missense NM_001407908.1:c.5041G>C NP_001394837.1:p.Ala1681Pro missense NM_001407909.1:c.5041G>C NP_001394838.1:p.Ala1681Pro missense NM_001407910.1:c.5041G>C NP_001394839.1:p.Ala1681Pro missense NM_001407915.1:c.5038G>C NP_001394844.1:p.Ala1680Pro missense NM_001407916.1:c.5038G>C NP_001394845.1:p.Ala1680Pro missense NM_001407917.1:c.5038G>C NP_001394846.1:p.Ala1680Pro missense NM_001407918.1:c.5038G>C NP_001394847.1:p.Ala1680Pro missense NM_001407919.1:c.5131G>C NP_001394848.1:p.Ala1711Pro missense NM_001407920.1:c.4990G>C NP_001394849.1:p.Ala1664Pro missense NM_001407921.1:c.4990G>C NP_001394850.1:p.Ala1664Pro missense NM_001407922.1:c.4990G>C NP_001394851.1:p.Ala1664Pro missense NM_001407923.1:c.4990G>C NP_001394852.1:p.Ala1664Pro missense NM_001407924.1:c.4990G>C NP_001394853.1:p.Ala1664Pro missense NM_001407925.1:c.4990G>C NP_001394854.1:p.Ala1664Pro missense NM_001407926.1:c.4990G>C NP_001394855.1:p.Ala1664Pro missense NM_001407927.1:c.4987G>C NP_001394856.1:p.Ala1663Pro missense NM_001407928.1:c.4987G>C NP_001394857.1:p.Ala1663Pro missense NM_001407929.1:c.4987G>C NP_001394858.1:p.Ala1663Pro missense NM_001407930.1:c.4987G>C NP_001394859.1:p.Ala1663Pro missense NM_001407931.1:c.4987G>C NP_001394860.1:p.Ala1663Pro missense NM_001407932.1:c.4987G>C NP_001394861.1:p.Ala1663Pro missense NM_001407933.1:c.4987G>C NP_001394862.1:p.Ala1663Pro missense NM_001407934.1:c.4984G>C NP_001394863.1:p.Ala1662Pro missense NM_001407935.1:c.4984G>C NP_001394864.1:p.Ala1662Pro missense NM_001407936.1:c.4984G>C NP_001394865.1:p.Ala1662Pro missense NM_001407937.1:c.5131G>C NP_001394866.1:p.Ala1711Pro missense NM_001407938.1:c.5131G>C NP_001394867.1:p.Ala1711Pro missense NM_001407939.1:c.5128G>C NP_001394868.1:p.Ala1710Pro missense NM_001407940.1:c.5128G>C NP_001394869.1:p.Ala1710Pro missense NM_001407941.1:c.5125G>C NP_001394870.1:p.Ala1709Pro missense NM_001407942.1:c.5113G>C NP_001394871.1:p.Ala1705Pro missense NM_001407943.1:c.5110G>C NP_001394872.1:p.Ala1704Pro missense NM_001407944.1:c.5110G>C NP_001394873.1:p.Ala1704Pro missense NM_001407945.1:c.5110G>C NP_001394874.1:p.Ala1704Pro missense NM_001407946.1:c.4921G>C NP_001394875.1:p.Ala1641Pro missense NM_001407947.1:c.4921G>C NP_001394876.1:p.Ala1641Pro missense NM_001407948.1:c.4921G>C NP_001394877.1:p.Ala1641Pro missense NM_001407949.1:c.4921G>C NP_001394878.1:p.Ala1641Pro missense NM_001407950.1:c.4918G>C NP_001394879.1:p.Ala1640Pro missense NM_001407951.1:c.4918G>C NP_001394880.1:p.Ala1640Pro missense NM_001407952.1:c.4918G>C NP_001394881.1:p.Ala1640Pro missense NM_001407953.1:c.4918G>C NP_001394882.1:p.Ala1640Pro missense NM_001407954.1:c.4918G>C NP_001394883.1:p.Ala1640Pro missense NM_001407955.1:c.4918G>C NP_001394884.1:p.Ala1640Pro missense NM_001407956.1:c.4915G>C NP_001394885.1:p.Ala1639Pro missense NM_001407957.1:c.4915G>C NP_001394886.1:p.Ala1639Pro missense NM_001407958.1:c.4915G>C NP_001394887.1:p.Ala1639Pro missense NM_001407959.1:c.4873G>C NP_001394888.1:p.Ala1625Pro missense NM_001407960.1:c.4870G>C NP_001394889.1:p.Ala1624Pro missense NM_001407962.1:c.4870G>C NP_001394891.1:p.Ala1624Pro missense NM_001407963.1:c.4867G>C NP_001394892.1:p.Ala1623Pro missense NM_001407964.1:c.4792G>C NP_001394893.1:p.Ala1598Pro missense NM_001407965.1:c.4747G>C NP_001394894.1:p.Ala1583Pro missense NM_001407966.1:c.4366G>C NP_001394895.1:p.Ala1456Pro missense NM_001407967.1:c.4363G>C NP_001394896.1:p.Ala1455Pro missense NM_001407968.1:c.2650G>C NP_001394897.1:p.Ala884Pro missense NM_001407969.1:c.2647G>C NP_001394898.1:p.Ala883Pro missense NM_001407970.1:c.2011G>C NP_001394899.1:p.Ala671Pro missense NM_001407971.1:c.2011G>C NP_001394900.1:p.Ala671Pro missense NM_001407972.1:c.2008G>C NP_001394901.1:p.Ala670Pro missense NM_001407973.1:c.1945G>C NP_001394902.1:p.Ala649Pro missense NM_001407974.1:c.1945G>C NP_001394903.1:p.Ala649Pro missense NM_001407975.1:c.1945G>C NP_001394904.1:p.Ala649Pro missense NM_001407976.1:c.1945G>C NP_001394905.1:p.Ala649Pro missense NM_001407977.1:c.1945G>C NP_001394906.1:p.Ala649Pro missense NM_001407978.1:c.1945G>C NP_001394907.1:p.Ala649Pro missense NM_001407979.1:c.1942G>C NP_001394908.1:p.Ala648Pro missense NM_001407980.1:c.1942G>C NP_001394909.1:p.Ala648Pro missense NM_001407981.1:c.1942G>C NP_001394910.1:p.Ala648Pro missense NM_001407982.1:c.1942G>C NP_001394911.1:p.Ala648Pro missense NM_001407983.1:c.1942G>C NP_001394912.1:p.Ala648Pro missense NM_001407984.1:c.1942G>C NP_001394913.1:p.Ala648Pro missense NM_001407985.1:c.1942G>C NP_001394914.1:p.Ala648Pro missense NM_001407986.1:c.1942G>C NP_001394915.1:p.Ala648Pro missense NM_001407990.1:c.1942G>C NP_001394919.1:p.Ala648Pro missense NM_001407991.1:c.1942G>C NP_001394920.1:p.Ala648Pro missense NM_001407992.1:c.1942G>C NP_001394921.1:p.Ala648Pro missense NM_001407993.1:c.1942G>C NP_001394922.1:p.Ala648Pro missense NM_001408392.1:c.1939G>C NP_001395321.1:p.Ala647Pro missense NM_001408396.1:c.1939G>C NP_001395325.1:p.Ala647Pro missense NM_001408397.1:c.1939G>C NP_001395326.1:p.Ala647Pro missense NM_001408398.1:c.1939G>C NP_001395327.1:p.Ala647Pro missense NM_001408399.1:c.1939G>C NP_001395328.1:p.Ala647Pro missense NM_001408400.1:c.1939G>C NP_001395329.1:p.Ala647Pro missense NM_001408401.1:c.1939G>C NP_001395330.1:p.Ala647Pro missense NM_001408402.1:c.1939G>C NP_001395331.1:p.Ala647Pro missense NM_001408403.1:c.1939G>C NP_001395332.1:p.Ala647Pro missense NM_001408404.1:c.1939G>C NP_001395333.1:p.Ala647Pro missense NM_001408406.1:c.1936G>C NP_001395335.1:p.Ala646Pro missense NM_001408407.1:c.1936G>C NP_001395336.1:p.Ala646Pro missense NM_001408408.1:c.1936G>C NP_001395337.1:p.Ala646Pro missense NM_001408409.1:c.1933G>C NP_001395338.1:p.Ala645Pro missense NM_001408410.1:c.1870G>C NP_001395339.1:p.Ala624Pro missense NM_001408411.1:c.1867G>C NP_001395340.1:p.Ala623Pro missense NM_001408412.1:c.1864G>C NP_001395341.1:p.Ala622Pro missense NM_001408413.1:c.1864G>C NP_001395342.1:p.Ala622Pro missense NM_001408414.1:c.1864G>C NP_001395343.1:p.Ala622Pro missense NM_001408415.1:c.1864G>C NP_001395344.1:p.Ala622Pro missense NM_001408416.1:c.1864G>C NP_001395345.1:p.Ala622Pro missense NM_001408418.1:c.1828G>C NP_001395347.1:p.Ala610Pro missense NM_001408419.1:c.1828G>C NP_001395348.1:p.Ala610Pro missense NM_001408420.1:c.1828G>C NP_001395349.1:p.Ala610Pro missense NM_001408421.1:c.1825G>C NP_001395350.1:p.Ala609Pro missense NM_001408422.1:c.1825G>C NP_001395351.1:p.Ala609Pro missense NM_001408423.1:c.1825G>C NP_001395352.1:p.Ala609Pro missense NM_001408424.1:c.1825G>C NP_001395353.1:p.Ala609Pro missense NM_001408425.1:c.1822G>C NP_001395354.1:p.Ala608Pro missense NM_001408426.1:c.1822G>C NP_001395355.1:p.Ala608Pro missense NM_001408427.1:c.1822G>C NP_001395356.1:p.Ala608Pro missense NM_001408428.1:c.1822G>C NP_001395357.1:p.Ala608Pro missense NM_001408429.1:c.1822G>C NP_001395358.1:p.Ala608Pro missense NM_001408430.1:c.1822G>C NP_001395359.1:p.Ala608Pro missense NM_001408431.1:c.1822G>C NP_001395360.1:p.Ala608Pro missense NM_001408432.1:c.1819G>C NP_001395361.1:p.Ala607Pro missense NM_001408433.1:c.1819G>C NP_001395362.1:p.Ala607Pro missense NM_001408434.1:c.1819G>C NP_001395363.1:p.Ala607Pro missense NM_001408435.1:c.1819G>C NP_001395364.1:p.Ala607Pro missense NM_001408436.1:c.1819G>C NP_001395365.1:p.Ala607Pro missense NM_001408437.1:c.1819G>C NP_001395366.1:p.Ala607Pro missense NM_001408438.1:c.1819G>C NP_001395367.1:p.Ala607Pro missense NM_001408439.1:c.1819G>C NP_001395368.1:p.Ala607Pro missense NM_001408440.1:c.1819G>C NP_001395369.1:p.Ala607Pro missense NM_001408441.1:c.1819G>C NP_001395370.1:p.Ala607Pro missense NM_001408442.1:c.1819G>C NP_001395371.1:p.Ala607Pro missense NM_001408443.1:c.1819G>C NP_001395372.1:p.Ala607Pro missense NM_001408444.1:c.1819G>C NP_001395373.1:p.Ala607Pro missense NM_001408445.1:c.1816G>C NP_001395374.1:p.Ala606Pro missense NM_001408446.1:c.1816G>C NP_001395375.1:p.Ala606Pro missense NM_001408447.1:c.1816G>C NP_001395376.1:p.Ala606Pro missense NM_001408448.1:c.1816G>C NP_001395377.1:p.Ala606Pro missense NM_001408450.1:c.1816G>C NP_001395379.1:p.Ala606Pro missense NM_001408451.1:c.1810G>C NP_001395380.1:p.Ala604Pro missense NM_001408452.1:c.1804G>C NP_001395381.1:p.Ala602Pro missense NM_001408453.1:c.1804G>C NP_001395382.1:p.Ala602Pro missense NM_001408454.1:c.1804G>C NP_001395383.1:p.Ala602Pro missense NM_001408455.1:c.1804G>C NP_001395384.1:p.Ala602Pro missense NM_001408456.1:c.1804G>C NP_001395385.1:p.Ala602Pro missense NM_001408457.1:c.1804G>C NP_001395386.1:p.Ala602Pro missense NM_001408458.1:c.1801G>C NP_001395387.1:p.Ala601Pro missense NM_001408459.1:c.1801G>C NP_001395388.1:p.Ala601Pro missense NM_001408460.1:c.1801G>C NP_001395389.1:p.Ala601Pro missense NM_001408461.1:c.1801G>C NP_001395390.1:p.Ala601Pro missense NM_001408462.1:c.1801G>C NP_001395391.1:p.Ala601Pro missense NM_001408463.1:c.1801G>C NP_001395392.1:p.Ala601Pro missense NM_001408464.1:c.1801G>C NP_001395393.1:p.Ala601Pro missense NM_001408465.1:c.1801G>C NP_001395394.1:p.Ala601Pro missense NM_001408466.1:c.1801G>C NP_001395395.1:p.Ala601Pro missense NM_001408467.1:c.1801G>C NP_001395396.1:p.Ala601Pro missense NM_001408468.1:c.1798G>C NP_001395397.1:p.Ala600Pro missense NM_001408469.1:c.1798G>C NP_001395398.1:p.Ala600Pro missense NM_001408470.1:c.1798G>C NP_001395399.1:p.Ala600Pro missense NM_001408472.1:c.1942G>C NP_001395401.1:p.Ala648Pro missense NM_001408473.1:c.1939G>C NP_001395402.1:p.Ala647Pro missense NM_001408474.1:c.1744G>C NP_001395403.1:p.Ala582Pro missense NM_001408475.1:c.1741G>C NP_001395404.1:p.Ala581Pro missense NM_001408476.1:c.1741G>C NP_001395405.1:p.Ala581Pro missense NM_001408478.1:c.1735G>C NP_001395407.1:p.Ala579Pro missense NM_001408479.1:c.1735G>C NP_001395408.1:p.Ala579Pro missense NM_001408480.1:c.1735G>C NP_001395409.1:p.Ala579Pro missense NM_001408481.1:c.1732G>C NP_001395410.1:p.Ala578Pro missense NM_001408482.1:c.1732G>C NP_001395411.1:p.Ala578Pro missense NM_001408483.1:c.1732G>C NP_001395412.1:p.Ala578Pro missense NM_001408484.1:c.1732G>C NP_001395413.1:p.Ala578Pro missense NM_001408485.1:c.1732G>C NP_001395414.1:p.Ala578Pro missense NM_001408489.1:c.1732G>C NP_001395418.1:p.Ala578Pro missense NM_001408490.1:c.1732G>C NP_001395419.1:p.Ala578Pro missense NM_001408491.1:c.1732G>C NP_001395420.1:p.Ala578Pro missense NM_001408492.1:c.1729G>C NP_001395421.1:p.Ala577Pro missense NM_001408493.1:c.1729G>C NP_001395422.1:p.Ala577Pro missense NM_001408494.1:c.1705G>C NP_001395423.1:p.Ala569Pro missense NM_001408495.1:c.1699G>C NP_001395424.1:p.Ala567Pro missense NM_001408496.1:c.1681G>C NP_001395425.1:p.Ala561Pro missense NM_001408497.1:c.1681G>C NP_001395426.1:p.Ala561Pro missense NM_001408498.1:c.1681G>C NP_001395427.1:p.Ala561Pro missense NM_001408499.1:c.1681G>C NP_001395428.1:p.Ala561Pro missense NM_001408500.1:c.1681G>C NP_001395429.1:p.Ala561Pro missense NM_001408501.1:c.1681G>C NP_001395430.1:p.Ala561Pro missense NM_001408502.1:c.1678G>C NP_001395431.1:p.Ala560Pro missense NM_001408503.1:c.1678G>C NP_001395432.1:p.Ala560Pro missense NM_001408504.1:c.1678G>C NP_001395433.1:p.Ala560Pro missense NM_001408505.1:c.1675G>C NP_001395434.1:p.Ala559Pro missense NM_001408506.1:c.1618G>C NP_001395435.1:p.Ala540Pro missense NM_001408507.1:c.1615G>C NP_001395436.1:p.Ala539Pro missense NM_001408508.1:c.1606G>C NP_001395437.1:p.Ala536Pro missense NM_001408509.1:c.1603G>C NP_001395438.1:p.Ala535Pro missense NM_001408510.1:c.1564G>C NP_001395439.1:p.Ala522Pro missense NM_001408511.1:c.1561G>C NP_001395440.1:p.Ala521Pro missense NM_001408512.1:c.1441G>C NP_001395441.1:p.Ala481Pro missense NM_001408513.1:c.1414G>C NP_001395442.1:p.Ala472Pro missense NM_001408514.1:c.1018G>C NP_001395443.1:p.Ala340Pro missense NM_007297.4:c.5113G>C NP_009228.2:p.Ala1705Pro missense NM_007298.4:c.1942G>C NP_009229.2:p.Ala648Pro missense NM_007299.4:c.1942G>C NP_009230.2:p.Ala648Pro missense NM_007300.4:c.5317G>C NP_009231.2:p.Ala1773Pro missense NM_007304.2:c.1942G>C NP_009235.2:p.Ala648Pro missense NR_027676.2:n.5431G>C non-coding transcript variant NC_000017.11:g.43057075C>G NC_000017.10:g.41209092C>G NG_005905.2:g.160909G>C LRG_292:g.160909G>C LRG_292t1:c.5254G>C LRG_292p1:p.Ala1752Pro U14680.1:n.5373G>C - Protein change
- A1752P, A648P, A1705P, A1773P, A1639P, A1640P, A1641P, A1683P, A1703P, A1708P, A1725P, A1732P, A1748P, A1750P, A481P, A522P, A535P, A560P, A601P, A608P, A610P, A670P, A884P, A1455P, A1624P, A1625P, A1662P, A1680P, A1682P, A1704P, A1710P, A472P, A539P, A540P, A569P, A577P, A578P, A582P, A604P, A609P, A622P, A646P, A883P, A1583P, A1598P, A1664P, A1684P, A1709P, A1724P, A1726P, A1747P, A1751P, A1772P, A581P, A600P, A602P, A607P, A623P, A649P, A671P, A1456P, A1623P, A1663P, A1681P, A1685P, A1711P, A1733P, A1749P, A1774P, A340P, A521P, A536P, A559P, A561P, A567P, A579P, A606P, A624P, A645P, A647P
- Other names
- -
- Canonical SPDI
- NC_000017.11:43057074:C:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- functionally_abnormal Sequence Ontology [SO:0002218]
- The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5254G>C, a MISSENSE variant, produced a function score of -3.13, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. [submitted by Brotman Baty Institute, University of Washington]
-
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.
-
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 | ||
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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 |
13029 | 14833 |
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. |
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Uncertain significance (2) |
no assertion criteria provided
|
Nov 17, 1998 | RCV000112581.7 | |
Pathogenic (1) |
criteria provided, single submitter
|
Jun 3, 2022 | RCV000563666.6 | |
Likely pathogenic (1) |
criteria provided, single submitter
|
Dec 14, 2023 | RCV001326888.10 | |
Likely pathogenic (1) |
criteria provided, single submitter
|
Aug 15, 2023 | RCV003321495.2 |
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. |
|
---|---|---|---|---|---|
Likely 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: SCV004026748.1
First in ClinVar: Aug 19, 2023 Last updated: Aug 19, 2023 |
|
|
Pathogenic
(Jun 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000665879.5
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
The p.A1752P pathogenic variant (also known as c.5254G>C and 5373G>C), located in coding exon 18 of the BRCA1 gene, results from a G to C … (more)
The p.A1752P pathogenic variant (also known as c.5254G>C and 5373G>C), located in coding exon 18 of the BRCA1 gene, results from a G to C substitution at nucleotide position 5254. The alanine at codon 1752 is replaced by proline, an amino acid with highly similar properties. This alteration has been reported in multiple women with early-onset breast cancer as well as family histories of breast cancer, including multiple reports in Chinese cohorts (Gao X et al. Hum Mutat, 2020 03;41:696-708; Bhaskaran SP et al. Int J Cancer, 2019 08;145:962-973; Li WF et al. Breast Cancer Res Treat, 2008 Jul;110:99-109; Essioux L et al. Am. J. Med. Genet. 1998 Sep;79:175-83; Bergthorsson JT et al. J. Med. Genet. 2001 Jun;38:361-8). Multiple assays find this variant is non-functional (Findlay GM et al. Nature, 2018 10;562:217-222; Lee MS et al. Cancer Res. 2010 Jun;70:4880-90; Phelan CM et al. J. Med. Genet., 2005 Feb;42:138-46). Based on literature and internal structural assessments, this alteration is structurally detrimental by breaking an alpha helix in BRCT domains (Ambry internal data; Karchin R et al. PLoS Comput Biol, 2007 Feb;3:e26; Clapperton JA et al. Nat. Struct. Mol. Biol., 2004 Jun;11:512-8). In addition, this alteration segregated with disease and was associated with family and tumor features that characterize a pathogenic mutation in BRCA1 (Caputo SM et al. Am J Hum Genet, 2021 10;108:1907-1923). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
|
|
Likely pathogenic
(Dec 14, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001517941.4
First in ClinVar: Mar 14, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1752 of the BRCA1 protein (p.Ala1752Pro). … (more)
This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1752 of the BRCA1 protein (p.Ala1752Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 9788557, 11389159, 17851763, 30702160, 31825140). This variant is also known as 5373C>G. ClinVar contains an entry for this variant (Variation ID: 55483). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is expected to disrupt BRCA1 function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 14534301, 15172985, 15689452, 17305420, 20516115, 30209399). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
|
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Uncertain significance
(Nov 17, 1998)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145414.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 1
Geographic origin: France
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: Black
Geographic origin: France
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: Caucasian
Geographic origin: Denmark
|
|
not provided
(-)
|
no classification provided
Method: in vitro
|
Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
|
Brotman Baty Institute, University of Washington
Accession: SCV001242955.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-3.12678112656794
|
Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
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A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
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A brief description of the result of this method for this variant. |
Submitter
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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
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This column includes more information supporting functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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functionally_abnormal
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001242955.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5254G>C, a MISSENSE variant, produced a function score of -3.13, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5254G>C, a MISSENSE variant, produced a function score of -3.13, corresponding to a functional classification of LOSS_OF_FUNCTION. SGE function score ranges for classification are as follows: ‘functional’, score > -0.748; ‘intermediate’, -0.748 > score > -1.328; ‘non-functional’, score < -1.328. The median synonymous SNV scored 0.0 and the median nonsense SNV scored -2.12. (less)
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Classification of 101 BRCA1 and BRCA2 variants of uncertain significance by cosegregation study: A powerful approach. | Caputo SM | American journal of human genetics | 2021 | PMID: 34597585 |
Comprehensive profiling of BRCA1 and BRCA2 variants in breast and ovarian cancer in Chinese patients. | Gao X | Human mutation | 2020 | PMID: 31825140 |
Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients. | Bhaskaran SP | International journal of cancer | 2019 | PMID: 30702160 |
Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
Functional assays provide a robust tool for the clinical annotation of genetic variants of uncertain significance. | Woods NT | NPJ genomic medicine | 2016 | PMID: 28781887 |
Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. | Lee MS | Cancer research | 2010 | PMID: 20516115 |
The prevalence of BRCA1 and BRCA2 germline mutations in high-risk breast cancer patients of Chinese Han nationality: two recurrent mutations were identified. | Li WF | Breast cancer research and treatment | 2008 | PMID: 17851763 |
Functional impact of missense variants in BRCA1 predicted by supervised learning. | Karchin R | PLoS computational biology | 2007 | PMID: 17305420 |
Insights into the molecular basis of human hereditary breast cancer from studies of the BRCA1 BRCT domain. | Glover JN | Familial cancer | 2006 | PMID: 16528612 |
Classification of BRCA1 missense variants of unknown clinical significance. | Phelan CM | Journal of medical genetics | 2005 | PMID: 15689452 |
Structure-based assessment of missense mutations in human BRCA1: implications for breast and ovarian cancer predisposition. | Mirkovic N | Cancer research | 2004 | PMID: 15172985 |
Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. | Clapperton JA | Nature structural & molecular biology | 2004 | PMID: 15133502 |
Detection of protein folding defects caused by BRCA1-BRCT truncation and missense mutations. | Williams RS | The Journal of biological chemistry | 2003 | PMID: 14534301 |
BRCA1 and BRCA2 mutation status and cancer family history of Danish women affected with multifocal or bilateral breast cancer at a young age. | Bergthorsson JT | Journal of medical genetics | 2001 | PMID: 11389159 |
Marker segregation information in breast/ovarian cancer genetic counseling: is it still useful? Groupe Génétique et Cancer de la Fédération Nationale des Centres de Lutte Contre le Cancer. | Essioux L | American journal of medical genetics | 1998 | PMID: 9788557 |
https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
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Text-mined citations for rs80357074 ...
HelpRecord last updated Oct 08, 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.