ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5365G>T (p.Ala1789Ser)
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.
Uncertain significance(7); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_007294.4(BRCA1):c.5365G>T (p.Ala1789Ser)
Variation ID: 55553 Accession: VCV000055553.29
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43049162 (GRCh38) [ NCBI UCSC ] 17: 41201179 (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 Aug 11, 2024 May 24, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_007294.4:c.5365G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Ala1789Ser missense NM_001407571.1:c.5152G>T NP_001394500.1:p.Ala1718Ser missense NM_001407581.1:c.5431G>T NP_001394510.1:p.Ala1811Ser missense NM_001407582.1:c.5431G>T NP_001394511.1:p.Ala1811Ser missense NM_001407583.1:c.5428G>T NP_001394512.1:p.Ala1810Ser missense NM_001407585.1:c.5428G>T NP_001394514.1:p.Ala1810Ser missense NM_001407587.1:c.5428G>T NP_001394516.1:p.Ala1810Ser missense NM_001407590.1:c.5425G>T NP_001394519.1:p.Ala1809Ser missense NM_001407591.1:c.5425G>T NP_001394520.1:p.Ala1809Ser missense NM_001407593.1:c.5365G>T NP_001394522.1:p.Ala1789Ser missense NM_001407594.1:c.5365G>T NP_001394523.1:p.Ala1789Ser missense NM_001407596.1:c.5365G>T NP_001394525.1:p.Ala1789Ser missense NM_001407597.1:c.5365G>T NP_001394526.1:p.Ala1789Ser missense NM_001407598.1:c.5365G>T NP_001394527.1:p.Ala1789Ser missense NM_001407602.1:c.5365G>T NP_001394531.1:p.Ala1789Ser missense NM_001407603.1:c.5365G>T NP_001394532.1:p.Ala1789Ser missense NM_001407605.1:c.5365G>T NP_001394534.1:p.Ala1789Ser missense NM_001407610.1:c.5362G>T NP_001394539.1:p.Ala1788Ser missense NM_001407611.1:c.5362G>T NP_001394540.1:p.Ala1788Ser missense NM_001407612.1:c.5362G>T NP_001394541.1:p.Ala1788Ser missense NM_001407613.1:c.5362G>T NP_001394542.1:p.Ala1788Ser missense NM_001407614.1:c.5362G>T NP_001394543.1:p.Ala1788Ser missense NM_001407615.1:c.5362G>T NP_001394544.1:p.Ala1788Ser missense NM_001407616.1:c.5362G>T NP_001394545.1:p.Ala1788Ser missense NM_001407617.1:c.5362G>T NP_001394546.1:p.Ala1788Ser missense NM_001407618.1:c.5362G>T NP_001394547.1:p.Ala1788Ser missense NM_001407619.1:c.5362G>T NP_001394548.1:p.Ala1788Ser missense NM_001407620.1:c.5362G>T NP_001394549.1:p.Ala1788Ser missense NM_001407621.1:c.5362G>T NP_001394550.1:p.Ala1788Ser missense NM_001407622.1:c.5362G>T NP_001394551.1:p.Ala1788Ser missense NM_001407623.1:c.5362G>T NP_001394552.1:p.Ala1788Ser missense NM_001407624.1:c.5362G>T NP_001394553.1:p.Ala1788Ser missense NM_001407625.1:c.5362G>T NP_001394554.1:p.Ala1788Ser missense NM_001407626.1:c.5362G>T NP_001394555.1:p.Ala1788Ser missense NM_001407627.1:c.5359G>T NP_001394556.1:p.Ala1787Ser missense NM_001407628.1:c.5359G>T NP_001394557.1:p.Ala1787Ser missense NM_001407629.1:c.5359G>T NP_001394558.1:p.Ala1787Ser missense NM_001407630.1:c.5359G>T NP_001394559.1:p.Ala1787Ser missense NM_001407631.1:c.5359G>T NP_001394560.1:p.Ala1787Ser missense NM_001407632.1:c.5359G>T NP_001394561.1:p.Ala1787Ser missense NM_001407633.1:c.5359G>T NP_001394562.1:p.Ala1787Ser missense NM_001407634.1:c.5359G>T NP_001394563.1:p.Ala1787Ser missense NM_001407635.1:c.5359G>T NP_001394564.1:p.Ala1787Ser missense NM_001407636.1:c.5359G>T NP_001394565.1:p.Ala1787Ser missense NM_001407637.1:c.5359G>T NP_001394566.1:p.Ala1787Ser missense NM_001407638.1:c.5359G>T NP_001394567.1:p.Ala1787Ser missense NM_001407639.1:c.5359G>T NP_001394568.1:p.Ala1787Ser missense NM_001407640.1:c.5359G>T NP_001394569.1:p.Ala1787Ser missense NM_001407641.1:c.5359G>T NP_001394570.1:p.Ala1787Ser missense NM_001407642.1:c.5359G>T NP_001394571.1:p.Ala1787Ser missense NM_001407644.1:c.5356G>T NP_001394573.1:p.Ala1786Ser missense NM_001407645.1:c.5356G>T NP_001394574.1:p.Ala1786Ser missense NM_001407646.1:c.5353G>T NP_001394575.1:p.Ala1785Ser missense NM_001407647.1:c.5350G>T NP_001394576.1:p.Ala1784Ser missense NM_001407648.1:c.5308G>T NP_001394577.1:p.Ala1770Ser missense NM_001407649.1:c.5305G>T NP_001394578.1:p.Ala1769Ser missense NM_001407652.1:c.5287G>T NP_001394581.1:p.Ala1763Ser missense NM_001407653.1:c.5287G>T NP_001394582.1:p.Ala1763Ser missense NM_001407654.1:c.5287G>T NP_001394583.1:p.Ala1763Ser missense NM_001407655.1:c.5287G>T NP_001394584.1:p.Ala1763Ser missense NM_001407656.1:c.5284G>T NP_001394585.1:p.Ala1762Ser missense NM_001407657.1:c.5284G>T NP_001394586.1:p.Ala1762Ser missense NM_001407658.1:c.5284G>T NP_001394587.1:p.Ala1762Ser missense NM_001407659.1:c.5281G>T NP_001394588.1:p.Ala1761Ser missense NM_001407660.1:c.5281G>T NP_001394589.1:p.Ala1761Ser missense NM_001407661.1:c.5281G>T NP_001394590.1:p.Ala1761Ser missense NM_001407662.1:c.5281G>T NP_001394591.1:p.Ala1761Ser missense NM_001407663.1:c.5281G>T NP_001394592.1:p.Ala1761Ser missense NM_001407664.1:c.5242G>T NP_001394593.1:p.Ala1748Ser missense NM_001407665.1:c.5242G>T NP_001394594.1:p.Ala1748Ser missense NM_001407666.1:c.5242G>T NP_001394595.1:p.Ala1748Ser missense NM_001407667.1:c.5242G>T NP_001394596.1:p.Ala1748Ser missense NM_001407668.1:c.5242G>T NP_001394597.1:p.Ala1748Ser missense NM_001407669.1:c.5242G>T NP_001394598.1:p.Ala1748Ser missense NM_001407670.1:c.5239G>T NP_001394599.1:p.Ala1747Ser missense NM_001407671.1:c.5239G>T NP_001394600.1:p.Ala1747Ser missense NM_001407672.1:c.5239G>T NP_001394601.1:p.Ala1747Ser missense NM_001407673.1:c.5239G>T NP_001394602.1:p.Ala1747Ser missense NM_001407674.1:c.5239G>T NP_001394603.1:p.Ala1747Ser missense NM_001407675.1:c.5239G>T NP_001394604.1:p.Ala1747Ser missense NM_001407676.1:c.5239G>T NP_001394605.1:p.Ala1747Ser missense NM_001407677.1:c.5239G>T NP_001394606.1:p.Ala1747Ser missense NM_001407678.1:c.5239G>T NP_001394607.1:p.Ala1747Ser missense NM_001407679.1:c.5239G>T NP_001394608.1:p.Ala1747Ser missense NM_001407680.1:c.5239G>T NP_001394609.1:p.Ala1747Ser missense NM_001407681.1:c.5236G>T NP_001394610.1:p.Ala1746Ser missense NM_001407682.1:c.5236G>T NP_001394611.1:p.Ala1746Ser missense NM_001407683.1:c.5236G>T NP_001394612.1:p.Ala1746Ser missense NM_001407685.1:c.5236G>T NP_001394614.1:p.Ala1746Ser missense NM_001407686.1:c.5236G>T NP_001394615.1:p.Ala1746Ser missense NM_001407687.1:c.5236G>T NP_001394616.1:p.Ala1746Ser missense NM_001407688.1:c.5236G>T NP_001394617.1:p.Ala1746Ser missense NM_001407689.1:c.5236G>T NP_001394618.1:p.Ala1746Ser missense NM_001407690.1:c.5233G>T NP_001394619.1:p.Ala1745Ser missense NM_001407691.1:c.5233G>T NP_001394620.1:p.Ala1745Ser missense NM_001407692.1:c.5224G>T NP_001394621.1:p.Ala1742Ser missense NM_001407694.1:c.5224G>T NP_001394623.1:p.Ala1742Ser missense NM_001407695.1:c.5224G>T NP_001394624.1:p.Ala1742Ser missense NM_001407696.1:c.5224G>T NP_001394625.1:p.Ala1742Ser missense NM_001407697.1:c.5224G>T NP_001394626.1:p.Ala1742Ser missense NM_001407698.1:c.5224G>T NP_001394627.1:p.Ala1742Ser missense NM_001407724.1:c.5224G>T NP_001394653.1:p.Ala1742Ser missense NM_001407725.1:c.5224G>T NP_001394654.1:p.Ala1742Ser missense NM_001407726.1:c.5224G>T NP_001394655.1:p.Ala1742Ser missense NM_001407727.1:c.5224G>T NP_001394656.1:p.Ala1742Ser missense NM_001407728.1:c.5224G>T NP_001394657.1:p.Ala1742Ser missense NM_001407729.1:c.5224G>T NP_001394658.1:p.Ala1742Ser missense NM_001407730.1:c.5224G>T NP_001394659.1:p.Ala1742Ser missense NM_001407731.1:c.5224G>T NP_001394660.1:p.Ala1742Ser missense NM_001407732.1:c.5221G>T NP_001394661.1:p.Ala1741Ser missense NM_001407733.1:c.5221G>T NP_001394662.1:p.Ala1741Ser missense NM_001407734.1:c.5221G>T NP_001394663.1:p.Ala1741Ser missense NM_001407735.1:c.5221G>T NP_001394664.1:p.Ala1741Ser missense NM_001407736.1:c.5221G>T NP_001394665.1:p.Ala1741Ser missense NM_001407737.1:c.5221G>T NP_001394666.1:p.Ala1741Ser missense NM_001407738.1:c.5221G>T NP_001394667.1:p.Ala1741Ser missense NM_001407739.1:c.5221G>T NP_001394668.1:p.Ala1741Ser missense NM_001407740.1:c.5221G>T NP_001394669.1:p.Ala1741Ser missense NM_001407741.1:c.5221G>T NP_001394670.1:p.Ala1741Ser missense NM_001407742.1:c.5221G>T NP_001394671.1:p.Ala1741Ser missense NM_001407743.1:c.5221G>T NP_001394672.1:p.Ala1741Ser missense NM_001407744.1:c.5221G>T NP_001394673.1:p.Ala1741Ser missense NM_001407745.1:c.5221G>T NP_001394674.1:p.Ala1741Ser missense NM_001407746.1:c.5221G>T NP_001394675.1:p.Ala1741Ser missense NM_001407747.1:c.5221G>T NP_001394676.1:p.Ala1741Ser missense NM_001407748.1:c.5221G>T NP_001394677.1:p.Ala1741Ser missense NM_001407749.1:c.5221G>T NP_001394678.1:p.Ala1741Ser missense NM_001407750.1:c.5221G>T NP_001394679.1:p.Ala1741Ser missense NM_001407751.1:c.5221G>T NP_001394680.1:p.Ala1741Ser missense NM_001407752.1:c.5221G>T NP_001394681.1:p.Ala1741Ser missense NM_001407838.1:c.5218G>T NP_001394767.1:p.Ala1740Ser missense NM_001407839.1:c.5218G>T NP_001394768.1:p.Ala1740Ser missense NM_001407841.1:c.5218G>T NP_001394770.1:p.Ala1740Ser missense NM_001407842.1:c.5218G>T NP_001394771.1:p.Ala1740Ser missense NM_001407843.1:c.5218G>T NP_001394772.1:p.Ala1740Ser missense NM_001407844.1:c.5218G>T NP_001394773.1:p.Ala1740Ser missense NM_001407845.1:c.5218G>T NP_001394774.1:p.Ala1740Ser missense NM_001407846.1:c.5218G>T NP_001394775.1:p.Ala1740Ser missense NM_001407847.1:c.5218G>T NP_001394776.1:p.Ala1740Ser missense NM_001407848.1:c.5218G>T NP_001394777.1:p.Ala1740Ser missense NM_001407849.1:c.5218G>T NP_001394778.1:p.Ala1740Ser missense NM_001407850.1:c.5218G>T NP_001394779.1:p.Ala1740Ser missense NM_001407851.1:c.5218G>T NP_001394780.1:p.Ala1740Ser missense NM_001407852.1:c.5218G>T NP_001394781.1:p.Ala1740Ser missense NM_001407853.1:c.5218G>T NP_001394782.1:p.Ala1740Ser missense NM_001407862.1:c.5164G>T NP_001394791.1:p.Ala1722Ser missense NM_001407863.1:c.5161G>T NP_001394792.1:p.Ala1721Ser missense NM_001407874.1:c.5158G>T NP_001394803.1:p.Ala1720Ser missense NM_001407875.1:c.5158G>T NP_001394804.1:p.Ala1720Ser missense NM_001407879.1:c.5155G>T NP_001394808.1:p.Ala1719Ser missense NM_001407881.1:c.5155G>T NP_001394810.1:p.Ala1719Ser missense NM_001407882.1:c.5155G>T NP_001394811.1:p.Ala1719Ser missense NM_001407884.1:c.5155G>T NP_001394813.1:p.Ala1719Ser missense NM_001407885.1:c.5155G>T NP_001394814.1:p.Ala1719Ser missense NM_001407886.1:c.5155G>T NP_001394815.1:p.Ala1719Ser missense NM_001407887.1:c.5155G>T NP_001394816.1:p.Ala1719Ser missense NM_001407889.1:c.5155G>T NP_001394818.1:p.Ala1719Ser missense NM_001407894.1:c.5152G>T NP_001394823.1:p.Ala1718Ser missense NM_001407895.1:c.5152G>T NP_001394824.1:p.Ala1718Ser missense NM_001407896.1:c.5152G>T NP_001394825.1:p.Ala1718Ser missense NM_001407897.1:c.5152G>T NP_001394826.1:p.Ala1718Ser missense NM_001407898.1:c.5152G>T NP_001394827.1:p.Ala1718Ser missense NM_001407899.1:c.5152G>T NP_001394828.1:p.Ala1718Ser missense NM_001407900.1:c.5152G>T NP_001394829.1:p.Ala1718Ser missense NM_001407902.1:c.5152G>T NP_001394831.1:p.Ala1718Ser missense NM_001407904.1:c.5152G>T NP_001394833.1:p.Ala1718Ser missense NM_001407906.1:c.5152G>T NP_001394835.1:p.Ala1718Ser missense NM_001407907.1:c.5152G>T NP_001394836.1:p.Ala1718Ser missense NM_001407908.1:c.5152G>T NP_001394837.1:p.Ala1718Ser missense NM_001407909.1:c.5152G>T NP_001394838.1:p.Ala1718Ser missense NM_001407910.1:c.5152G>T NP_001394839.1:p.Ala1718Ser missense NM_001407915.1:c.5149G>T NP_001394844.1:p.Ala1717Ser missense NM_001407916.1:c.5149G>T NP_001394845.1:p.Ala1717Ser missense NM_001407917.1:c.5149G>T NP_001394846.1:p.Ala1717Ser missense NM_001407918.1:c.5149G>T NP_001394847.1:p.Ala1717Ser missense NM_001407920.1:c.5101G>T NP_001394849.1:p.Ala1701Ser missense NM_001407921.1:c.5101G>T NP_001394850.1:p.Ala1701Ser missense NM_001407922.1:c.5101G>T NP_001394851.1:p.Ala1701Ser missense NM_001407923.1:c.5101G>T NP_001394852.1:p.Ala1701Ser missense NM_001407924.1:c.5101G>T NP_001394853.1:p.Ala1701Ser missense NM_001407925.1:c.5101G>T NP_001394854.1:p.Ala1701Ser missense NM_001407926.1:c.5101G>T NP_001394855.1:p.Ala1701Ser missense NM_001407927.1:c.5098G>T NP_001394856.1:p.Ala1700Ser missense NM_001407928.1:c.5098G>T NP_001394857.1:p.Ala1700Ser missense NM_001407929.1:c.5098G>T NP_001394858.1:p.Ala1700Ser missense NM_001407930.1:c.5098G>T NP_001394859.1:p.Ala1700Ser missense NM_001407931.1:c.5098G>T NP_001394860.1:p.Ala1700Ser missense NM_001407932.1:c.5098G>T NP_001394861.1:p.Ala1700Ser missense NM_001407933.1:c.5098G>T NP_001394862.1:p.Ala1700Ser missense NM_001407934.1:c.5095G>T NP_001394863.1:p.Ala1699Ser missense NM_001407935.1:c.5095G>T NP_001394864.1:p.Ala1699Ser missense NM_001407936.1:c.5095G>T NP_001394865.1:p.Ala1699Ser missense NM_001407946.1:c.5032G>T NP_001394875.1:p.Ala1678Ser missense NM_001407947.1:c.5032G>T NP_001394876.1:p.Ala1678Ser missense NM_001407948.1:c.5032G>T NP_001394877.1:p.Ala1678Ser missense NM_001407949.1:c.5032G>T NP_001394878.1:p.Ala1678Ser missense NM_001407950.1:c.5029G>T NP_001394879.1:p.Ala1677Ser missense NM_001407951.1:c.5029G>T NP_001394880.1:p.Ala1677Ser missense NM_001407952.1:c.5029G>T NP_001394881.1:p.Ala1677Ser missense NM_001407953.1:c.5029G>T NP_001394882.1:p.Ala1677Ser missense NM_001407954.1:c.5029G>T NP_001394883.1:p.Ala1677Ser missense NM_001407955.1:c.5029G>T NP_001394884.1:p.Ala1677Ser missense NM_001407956.1:c.5026G>T NP_001394885.1:p.Ala1676Ser missense NM_001407957.1:c.5026G>T NP_001394886.1:p.Ala1676Ser missense NM_001407958.1:c.5026G>T NP_001394887.1:p.Ala1676Ser missense NM_001407959.1:c.4984G>T NP_001394888.1:p.Ala1662Ser missense NM_001407960.1:c.4981G>T NP_001394889.1:p.Ala1661Ser missense NM_001407962.1:c.4981G>T NP_001394891.1:p.Ala1661Ser missense NM_001407963.1:c.4978G>T NP_001394892.1:p.Ala1660Ser missense NM_001407964.1:c.4903G>T NP_001394893.1:p.Ala1635Ser missense NM_001407965.1:c.4858G>T NP_001394894.1:p.Ala1620Ser missense NM_001407966.1:c.4477G>T NP_001394895.1:p.Ala1493Ser missense NM_001407967.1:c.4474G>T NP_001394896.1:p.Ala1492Ser missense NM_001407968.1:c.2761G>T NP_001394897.1:p.Ala921Ser missense NM_001407969.1:c.2758G>T NP_001394898.1:p.Ala920Ser missense NM_001407970.1:c.2122G>T NP_001394899.1:p.Ala708Ser missense NM_001407971.1:c.2122G>T NP_001394900.1:p.Ala708Ser missense NM_001407972.1:c.2119G>T NP_001394901.1:p.Ala707Ser missense NM_001407973.1:c.2056G>T NP_001394902.1:p.Ala686Ser missense NM_001407974.1:c.2056G>T NP_001394903.1:p.Ala686Ser missense NM_001407975.1:c.2056G>T NP_001394904.1:p.Ala686Ser missense NM_001407976.1:c.2056G>T NP_001394905.1:p.Ala686Ser missense NM_001407977.1:c.2056G>T NP_001394906.1:p.Ala686Ser missense NM_001407978.1:c.2056G>T NP_001394907.1:p.Ala686Ser missense NM_001407979.1:c.2053G>T NP_001394908.1:p.Ala685Ser missense NM_001407980.1:c.2053G>T NP_001394909.1:p.Ala685Ser missense NM_001407981.1:c.2053G>T NP_001394910.1:p.Ala685Ser missense NM_001407982.1:c.2053G>T NP_001394911.1:p.Ala685Ser missense NM_001407983.1:c.2053G>T NP_001394912.1:p.Ala685Ser missense NM_001407984.1:c.2053G>T NP_001394913.1:p.Ala685Ser missense NM_001407985.1:c.2053G>T NP_001394914.1:p.Ala685Ser missense NM_001407986.1:c.2053G>T NP_001394915.1:p.Ala685Ser missense NM_001407990.1:c.2053G>T NP_001394919.1:p.Ala685Ser missense NM_001407991.1:c.2053G>T NP_001394920.1:p.Ala685Ser missense NM_001407992.1:c.2053G>T NP_001394921.1:p.Ala685Ser missense NM_001407993.1:c.2053G>T NP_001394922.1:p.Ala685Ser missense NM_001408392.1:c.2050G>T NP_001395321.1:p.Ala684Ser missense NM_001408396.1:c.2050G>T NP_001395325.1:p.Ala684Ser missense NM_001408397.1:c.2050G>T NP_001395326.1:p.Ala684Ser missense NM_001408398.1:c.2050G>T NP_001395327.1:p.Ala684Ser missense NM_001408399.1:c.2050G>T NP_001395328.1:p.Ala684Ser missense NM_001408400.1:c.2050G>T NP_001395329.1:p.Ala684Ser missense NM_001408401.1:c.2050G>T NP_001395330.1:p.Ala684Ser missense NM_001408402.1:c.2050G>T NP_001395331.1:p.Ala684Ser missense NM_001408403.1:c.2050G>T NP_001395332.1:p.Ala684Ser missense NM_001408404.1:c.2050G>T NP_001395333.1:p.Ala684Ser missense NM_001408406.1:c.2047G>T NP_001395335.1:p.Ala683Ser missense NM_001408407.1:c.2047G>T NP_001395336.1:p.Ala683Ser missense NM_001408408.1:c.2047G>T NP_001395337.1:p.Ala683Ser missense NM_001408409.1:c.2044G>T NP_001395338.1:p.Ala682Ser missense NM_001408410.1:c.1981G>T NP_001395339.1:p.Ala661Ser missense NM_001408411.1:c.1978G>T NP_001395340.1:p.Ala660Ser missense NM_001408412.1:c.1975G>T NP_001395341.1:p.Ala659Ser missense NM_001408413.1:c.1975G>T NP_001395342.1:p.Ala659Ser missense NM_001408414.1:c.1975G>T NP_001395343.1:p.Ala659Ser missense NM_001408415.1:c.1975G>T NP_001395344.1:p.Ala659Ser missense NM_001408416.1:c.1975G>T NP_001395345.1:p.Ala659Ser missense NM_001408418.1:c.1939G>T NP_001395347.1:p.Ala647Ser missense NM_001408419.1:c.1939G>T NP_001395348.1:p.Ala647Ser missense NM_001408420.1:c.1939G>T NP_001395349.1:p.Ala647Ser missense NM_001408421.1:c.1936G>T NP_001395350.1:p.Ala646Ser missense NM_001408422.1:c.1936G>T NP_001395351.1:p.Ala646Ser missense NM_001408423.1:c.1936G>T NP_001395352.1:p.Ala646Ser missense NM_001408424.1:c.1936G>T NP_001395353.1:p.Ala646Ser missense NM_001408425.1:c.1933G>T NP_001395354.1:p.Ala645Ser missense NM_001408426.1:c.1933G>T NP_001395355.1:p.Ala645Ser missense NM_001408427.1:c.1933G>T NP_001395356.1:p.Ala645Ser missense NM_001408428.1:c.1933G>T NP_001395357.1:p.Ala645Ser missense NM_001408429.1:c.1933G>T NP_001395358.1:p.Ala645Ser missense NM_001408430.1:c.1933G>T NP_001395359.1:p.Ala645Ser missense NM_001408431.1:c.1933G>T NP_001395360.1:p.Ala645Ser missense NM_001408432.1:c.1930G>T NP_001395361.1:p.Ala644Ser missense NM_001408433.1:c.1930G>T NP_001395362.1:p.Ala644Ser missense NM_001408434.1:c.1930G>T NP_001395363.1:p.Ala644Ser missense NM_001408435.1:c.1930G>T NP_001395364.1:p.Ala644Ser missense NM_001408436.1:c.1930G>T NP_001395365.1:p.Ala644Ser missense NM_001408437.1:c.1930G>T NP_001395366.1:p.Ala644Ser missense NM_001408438.1:c.1930G>T NP_001395367.1:p.Ala644Ser missense NM_001408439.1:c.1930G>T NP_001395368.1:p.Ala644Ser missense NM_001408440.1:c.1930G>T NP_001395369.1:p.Ala644Ser missense NM_001408441.1:c.1930G>T NP_001395370.1:p.Ala644Ser missense NM_001408442.1:c.1930G>T NP_001395371.1:p.Ala644Ser missense NM_001408443.1:c.1930G>T NP_001395372.1:p.Ala644Ser missense NM_001408444.1:c.1930G>T NP_001395373.1:p.Ala644Ser missense NM_001408445.1:c.1927G>T NP_001395374.1:p.Ala643Ser missense NM_001408446.1:c.1927G>T NP_001395375.1:p.Ala643Ser missense NM_001408447.1:c.1927G>T NP_001395376.1:p.Ala643Ser missense NM_001408448.1:c.1927G>T NP_001395377.1:p.Ala643Ser missense NM_001408450.1:c.1927G>T NP_001395379.1:p.Ala643Ser missense NM_001408451.1:c.1921G>T NP_001395380.1:p.Ala641Ser missense NM_001408452.1:c.1915G>T NP_001395381.1:p.Ala639Ser missense NM_001408453.1:c.1915G>T NP_001395382.1:p.Ala639Ser missense NM_001408454.1:c.1915G>T NP_001395383.1:p.Ala639Ser missense NM_001408455.1:c.1915G>T NP_001395384.1:p.Ala639Ser missense NM_001408456.1:c.1915G>T NP_001395385.1:p.Ala639Ser missense NM_001408457.1:c.1915G>T NP_001395386.1:p.Ala639Ser missense NM_001408458.1:c.1912G>T NP_001395387.1:p.Ala638Ser missense NM_001408459.1:c.1912G>T NP_001395388.1:p.Ala638Ser missense NM_001408460.1:c.1912G>T NP_001395389.1:p.Ala638Ser missense NM_001408461.1:c.1912G>T NP_001395390.1:p.Ala638Ser missense NM_001408462.1:c.1912G>T NP_001395391.1:p.Ala638Ser missense NM_001408463.1:c.1912G>T NP_001395392.1:p.Ala638Ser missense NM_001408464.1:c.1912G>T NP_001395393.1:p.Ala638Ser missense NM_001408465.1:c.1912G>T NP_001395394.1:p.Ala638Ser missense NM_001408466.1:c.1912G>T NP_001395395.1:p.Ala638Ser missense NM_001408467.1:c.1912G>T NP_001395396.1:p.Ala638Ser missense NM_001408468.1:c.1909G>T NP_001395397.1:p.Ala637Ser missense NM_001408469.1:c.1909G>T NP_001395398.1:p.Ala637Ser missense NM_001408470.1:c.1909G>T NP_001395399.1:p.Ala637Ser missense NM_001408474.1:c.1855G>T NP_001395403.1:p.Ala619Ser missense NM_001408475.1:c.1852G>T NP_001395404.1:p.Ala618Ser missense NM_001408476.1:c.1852G>T NP_001395405.1:p.Ala618Ser missense NM_001408478.1:c.1846G>T NP_001395407.1:p.Ala616Ser missense NM_001408479.1:c.1846G>T NP_001395408.1:p.Ala616Ser missense NM_001408480.1:c.1846G>T NP_001395409.1:p.Ala616Ser missense NM_001408481.1:c.1843G>T NP_001395410.1:p.Ala615Ser missense NM_001408482.1:c.1843G>T NP_001395411.1:p.Ala615Ser missense NM_001408483.1:c.1843G>T NP_001395412.1:p.Ala615Ser missense NM_001408484.1:c.1843G>T NP_001395413.1:p.Ala615Ser missense NM_001408485.1:c.1843G>T NP_001395414.1:p.Ala615Ser missense NM_001408489.1:c.1843G>T NP_001395418.1:p.Ala615Ser missense NM_001408490.1:c.1843G>T NP_001395419.1:p.Ala615Ser missense NM_001408491.1:c.1843G>T NP_001395420.1:p.Ala615Ser missense NM_001408492.1:c.1840G>T NP_001395421.1:p.Ala614Ser missense NM_001408493.1:c.1840G>T NP_001395422.1:p.Ala614Ser missense NM_001408494.1:c.1816G>T NP_001395423.1:p.Ala606Ser missense NM_001408495.1:c.1810G>T NP_001395424.1:p.Ala604Ser missense NM_001408496.1:c.1792G>T NP_001395425.1:p.Ala598Ser missense NM_001408497.1:c.1792G>T NP_001395426.1:p.Ala598Ser missense NM_001408498.1:c.1792G>T NP_001395427.1:p.Ala598Ser missense NM_001408499.1:c.1792G>T NP_001395428.1:p.Ala598Ser missense NM_001408500.1:c.1792G>T NP_001395429.1:p.Ala598Ser missense NM_001408501.1:c.1792G>T NP_001395430.1:p.Ala598Ser missense NM_001408502.1:c.1789G>T NP_001395431.1:p.Ala597Ser missense NM_001408503.1:c.1789G>T NP_001395432.1:p.Ala597Ser missense NM_001408504.1:c.1789G>T NP_001395433.1:p.Ala597Ser missense NM_001408505.1:c.1786G>T NP_001395434.1:p.Ala596Ser missense NM_001408506.1:c.1729G>T NP_001395435.1:p.Ala577Ser missense NM_001408507.1:c.1726G>T NP_001395436.1:p.Ala576Ser missense NM_001408508.1:c.1717G>T NP_001395437.1:p.Ala573Ser missense NM_001408509.1:c.1714G>T NP_001395438.1:p.Ala572Ser missense NM_001408510.1:c.1675G>T NP_001395439.1:p.Ala559Ser missense NM_001408511.1:c.1672G>T NP_001395440.1:p.Ala558Ser missense NM_001408512.1:c.1552G>T NP_001395441.1:p.Ala518Ser missense NM_001408513.1:c.1525G>T NP_001395442.1:p.Ala509Ser missense NM_001408514.1:c.1129G>T NP_001395443.1:p.Ala377Ser missense NM_007297.4:c.5224G>T NP_009228.2:p.Ala1742Ser missense NM_007298.4:c.2053G>T NP_009229.2:p.Ala685Ser missense NM_007299.4:c.2021-1459G>T intron variant NM_007300.4:c.5428G>T NP_009231.2:p.Ala1810Ser missense NM_007304.2:c.2053G>T NP_009235.2:p.Ala685Ser missense NR_027676.2:n.5542G>T non-coding transcript variant NC_000017.11:g.43049162C>A NC_000017.10:g.41201179C>A NG_005905.2:g.168822G>T LRG_292:g.168822G>T LRG_292t1:c.5365G>T LRG_292p1:p.Ala1789Ser U14680.1:n.5484G>T - Protein change
- A1789S, A1810S, A685S, A1742S, A1741S, A1746S, A1763S, A1785S, A1786S, A377S, A509S, A572S, A596S, A1676S, A1701S, A1718S, A1740S, A558S, A598S, A618S, A639S, A659S, A683S, A707S, A921S, A1492S, A1661S, A1677S, A1699S, A1719S, A1747S, A1748S, A1761S, A1809S, A518S, A559S, A573S, A577S, A604S, A637S, A644S, A660S, A661S, A686S, A920S, A597S, A619S, A641S, A643S, A682S, A684S, A708S, A1620S, A1635S, A1660S, A1700S, A1720S, A1721S, A1722S, A1762S, A1769S, A1788S, A576S, A606S, A614S, A615S, A616S, A638S, A645S, A646S, A647S, A1493S, A1662S, A1678S, A1717S, A1745S, A1770S, A1784S, A1787S, A1811S
- Other names
- -
- Canonical SPDI
- NC_000017.11:43049161:C:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- functionally_normal Sequence Ontology [SO:0002219]
- The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5365G>T, a MISSENSE variant, produced a function score of -0.44, corresponding to a functional classification of FUNCTIONAL. 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 | ||
---|---|---|---|---|---|---|
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. |
---|---|---|---|---|
Conflicting interpretations of pathogenicity (5) |
criteria provided, conflicting classifications
|
Mar 7, 2023 | RCV000112629.19 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
|
Feb 1, 2023 | RCV000580957.16 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
|
Apr 9, 2024 | RCV001853023.15 | |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
|
May 24, 2024 | RCV001689610.17 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Oct 14, 2019 | RCV004017357.1 |
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. |
|
---|---|---|---|---|---|
Likely benign
(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: SCV000744585.1 First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
|
|
Likely benign
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002550942.4
First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023 |
|
|
Uncertain significance
(Feb 01, 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: SCV000683306.4
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces alanine with serine at codon 1789 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces alanine with serine at codon 1789 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have reported that this variant does no impact BRCA1 function in protein stability, phosphopeptide binding and specificity, transcription activation and homology-directed repair assays (PMID: 20516115, 28781887, 30257991) and in a haploid cell proliferation assay (PMID: 30209399) This variant has been reported in an individual affected with early-onset breast cancer with no family history of disease (PMID: 15887246). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same codon, c.5365G>A (p.Ala1789Thr), has been identified in individuals affected by breast and/or ovarian cancer (PMID: 18680205, 20737206, 30264118, 30287823, Color internal data) and has been reported to impair BRCA1 protein function in several functional studies (PMID: 18680205, 19493677, 20737206, 28781887, 29884841, 30209399, 32546644), suggesting that Ala at this position is important for the protein function. However, the same functional assays, that reported the p.Ala1789Thr variant to be defected, found our variant in question, p.Ala1789Ser, has no impact on BRCA1 function (PMID: 29884841, 30209399). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
|
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Uncertain Significance
(Mar 07, 2023)
|
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: SCV004817557.1
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 missense variant replaces alanine with serine at codon 1789 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on … (more)
This missense variant replaces alanine with serine at codon 1789 of the BRCA1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). Functional studies have reported that this variant does not impact BRCA1 function in transcription activation, homology-directed DNA repair, a haploid cell proliferation and structural stability assays (PMID: 20516115, 29884841, 30209399) and exhibits a moderate decrease in phosphopeptide binding and specificity assays (PMID: 20516115). This variant has been reported in an individual affected with early onset breast cancer with no family history (PMID: 15887246). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). A different variant affecting the same codon, c.5365G>A (p.Ala1789Thr), has been identified in individuals affected by breast and/or ovarian cancer (PMID: 18680205, 20737206, 30264118, 30287823, Color internal data) and has been reported to impair BRCA1 protein function in several functional studies (PMID: 18680205, 19493677, 20737206, 28781887, 29884841, 30209399, 32546644), suggesting that Ala at this position is important for the protein function. However, the same functional assays, that reported the p.Ala1789Thr variant to be defected, found our variant in question, p.Ala1789Ser, has no impact on BRCA1 function (PMID: 29884841, 30209399). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 1
|
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Likely benign
(Apr 27, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002645113.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
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Uncertain significance
(May 24, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV005184595.1
First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024 |
Comment:
Variant summary: BRCA1 c.5365G>T (p.Ala1789Ser) results in a conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign … (more)
Variant summary: BRCA1 c.5365G>T (p.Ala1789Ser) results in a conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251448 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.5365G>T has been reported in the literature in an individual affected with Hereditary Breast And Ovarian Cancer Syndrome (Bonadona_2005) without family history. This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Several publications report experimental evidence evaluating an impact on protein function, and show no significant impact on protein function (Woods_2016, Fernandes_2019, Petitalot_2019, Findlay_2018). The following publications have been ascertained in the context of this evaluation (PMID: 15887246, 30765603, 30209399, 30257991, 28781887). ClinVar contains an entry for this variant (Variation ID: 55553). Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
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Uncertain significance
(May 09, 2017)
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criteria provided, single submitter
Method: clinical testing
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Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000785154.2
First in ClinVar: May 30, 2018 Last updated: May 30, 2018 |
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Uncertain significance
(Dec 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV002313770.3
First in ClinVar: Mar 28, 2022 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1789 of the BRCA1 protein (p.Ala1789Ser). … (more)
This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1789 of the BRCA1 protein (p.Ala1789Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 15887246). ClinVar contains an entry for this variant (Variation ID: 55553). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (PMID: 30209399) indicates that this missense variant is not expected to disrupt BRCA1 function with a negative predictive value of 95%. Experimental studies have shown that this missense change does not substantially affect BRCA1 function (PMID: 20516115, 30257991, 30765603). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain Significance
(Oct 14, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV004848282.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 |
Comment:
Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Clinvar: LB (VKGL data-share consensus), VUS (Counsyl, Color, BIC - 1 individual). … (more)
Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Clinvar: LB (VKGL data-share consensus), VUS (Counsyl, Color, BIC - 1 individual). Not in gnomad. Reported in one individual with breast cancer at age 37 (Bonadona 2005). Functional and in silico assays classify variant as not pathogenic (Findlay 2018, Woods 2016, Lee 2010). One in silico study calls variant deleterious as a Serine at this position disrupts the BRCT superfamily conserved G[G/A] motif (Karchin 2008). (less)
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Uncertain significance
(Apr 09, 2024)
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criteria provided, single submitter
Method: curation
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Hereditary breast ovarian cancer syndrome
Affected status: not provided
Allele origin:
germline
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German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne
Accession: SCV005184348.1
First in ClinVar: Aug 11, 2024 Last updated: Aug 11, 2024 |
Comment:
According to the ClinGen ENIGMA BRCA1 v1.0.0 criteria we chose these criteria: PM2 (supporting pathogenic): Absent from controls , PP3 (supporting pathogenic): for missense or … (more)
According to the ClinGen ENIGMA BRCA1 v1.0.0 criteria we chose these criteria: PM2 (supporting pathogenic): Absent from controls , PP3 (supporting pathogenic): for missense or in-frame insertion, deletion or delins variants inside a (potentially) clinically important functional domain and predicted impact via proteinchange (BayesDel no-AF score ≥0.28). -> BayseDel no AF:0.3921, BP5 (medium benign): LR: 0,206541838 (Parson et al, 2019) (less)
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001906387.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Uncertain significance
(Dec 23, 2003)
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no assertion criteria provided
Method: clinical testing
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Breast-ovarian cancer, familial 1
Affected status: yes
Allele origin:
germline
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Breast Cancer Information Core (BIC) (BRCA1)
Accession: SCV000145483.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Number of individuals with the variant: 3
Ethnicity/Population group: Western European
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001953263.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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not provided
(-)
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no classification provided
Method: in vitro
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Breast-ovarian cancer, familial 1
Affected status: not applicable
Allele origin:
not applicable
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Brotman Baty Institute, University of Washington
Accession: SCV001243176.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
FUNCTIONAL:-0.439408021397876
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
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
Help
A brief description of the result of this method for 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 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_normal
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Method citation(s):
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Brotman Baty Institute, University of Washington
Accession: SCV001243176.1
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Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5365G>T, a MISSENSE variant, produced a function score of -0.44, corresponding to a functional classification of FUNCTIONAL. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5365G>T, a MISSENSE variant, produced a function score of -0.44, corresponding to a functional classification of FUNCTIONAL. 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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Functional Categorization of BRCA1 Variants of Uncertain Clinical Significance in Homologous Recombination Repair Complementation Assays. | Bouwman P | Clinical cancer research : an official journal of the American Association for Cancer Research | 2020 | PMID: 32546644 |
Impact of amino acid substitutions at secondary structures in the BRCT domains of the tumor suppressor BRCA1: Implications for clinical annotation. | Fernandes VC | The Journal of biological chemistry | 2019 | PMID: 30765603 |
Combining Homologous Recombination and Phosphopeptide-binding Data to Predict the Impact of BRCA1 BRCT Variants on Cancer Risk. | Petitalot A | Molecular cancer research : MCR | 2019 | PMID: 30257991 |
Comprehensive annotation of BRCA1 and BRCA2 missense variants by functionally validated sequence-based computational prediction models. | Hart SN | Genetics in medicine : official journal of the American College of Medical Genetics | 2019 | PMID: 29884841 |
Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls. | Momozawa Y | Nature communications | 2018 | PMID: 30287823 |
Prevalence of Variant Reclassification Following Hereditary Cancer Genetic Testing. | Mersch J | JAMA | 2018 | PMID: 30264118 |
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 |
Probing structure-function relationships in missense variants in the carboxy-terminal region of BRCA1. | Carvalho RS | PloS one | 2014 | PMID: 24845084 |
A recombination-based method to characterize human BRCA1 missense variants. | Guidugli L | Breast cancer research and treatment | 2011 | PMID: 20737206 |
Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. | Lee MS | Cancer research | 2010 | PMID: 20516115 |
Interlaboratory diagnostic validation of conformation-sensitive capillary electrophoresis for mutation scanning. | Mattocks CJ | Clinical chemistry | 2010 | PMID: 20167696 |
Characterisation of gene expression profiles of yeast cells expressing BRCA1 missense variants. | Di Cecco L | European journal of cancer (Oxford, England : 1990) | 2009 | PMID: 19493677 |
A yeast recombination assay to characterize human BRCA1 missense variants of unknown pathological significance. | Caligo MA | Human mutation | 2009 | PMID: 18680205 |
Functional impact of missense variants in BRCA1 predicted by supervised learning. | Karchin R | PLoS computational biology | 2007 | PMID: 17305420 |
A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2: application in a Dutch cancer clinic setting. | van der Hout AH | Human mutation | 2006 | PMID: 16683254 |
Application of embryonic lethal or other obvious phenotypes to characterize the clinical significance of genetic variants found in trans with known deleterious mutations. | Judkins T | Cancer research | 2005 | PMID: 16267036 |
Contribution of BRCA1 and BRCA2 germ-line mutations to the incidence of breast cancer in young women: results from a prospective population-based study in France. | Bonadona V | Genes, chromosomes & cancer | 2005 | PMID: 15887246 |
Evolution of the tumor suppressor BRCA1 locus in primates: implications for cancer predisposition. | Pavlicek A | Human molecular genetics | 2004 | PMID: 15385441 |
https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
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Text-mined citations for rs80357078 ...
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.