The BRCA1 c.5074G>A (p.Asp1692Asn) missense change affects the last nucleotide of exon 16 and is predicted to abolish the native splice donor site. An in vitro study demonstrated that this variant leads to multiple aberrant transcripts, including one causing exon 17 skipping and another causing activation of a cryptic splice donor site that leads to an in-frame retention of 153 bp of intron 17 (PMID: 25724305). These published findings are also supported by internal data. This variant has been reported in individuals with a personal and/or family history of breast and/or ovarian cancer (PMID: 8460636, 9452084, 10196379, 15571962). It is commonly reported in individuals of Icelandic ancestry and genetic linkage analysis suggests that this is an Icelandic founder mutation (PMID: 8460636, 9452084, 15571962). It is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as likely pathogenic.
ClinVar Genomic variation as it relates to human health
NM_007294.4(BRCA1):c.5074G>A (p.Asp1692Asn)
Germline
Classification
Help
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
Pathogenic/Likely pathogenic
9 out of 16 submissions contributed to this classification
Help
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.
16
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_007294.4(BRCA1):c.5074G>A (p.Asp1692Asn)
Variation ID: 37632 Accession: VCV000037632.43
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 17q21.31 17: 43067608 (GRCh38) [ NCBI UCSC ] 17: 41219625 (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 Apr 13, 2025 Mar 4, 2025 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_007294.4:c.5074G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_009225.1:p.Asp1692Asn missense NM_001407571.1:c.4861G>A NP_001394500.1:p.Asp1621Asn missense NM_001407581.1:c.5140G>A NP_001394510.1:p.Asp1714Asn missense NM_001407582.1:c.5140G>A NP_001394511.1:p.Asp1714Asn missense NM_001407583.1:c.5137G>A NP_001394512.1:p.Asp1713Asn missense NM_001407585.1:c.5137G>A NP_001394514.1:p.Asp1713Asn missense NM_001407587.1:c.5137G>A NP_001394516.1:p.Asp1713Asn missense NM_001407590.1:c.5134G>A NP_001394519.1:p.Asp1712Asn missense NM_001407591.1:c.5134G>A NP_001394520.1:p.Asp1712Asn missense NM_001407593.1:c.5074G>A NP_001394522.1:p.Asp1692Asn missense NM_001407594.1:c.5074G>A NP_001394523.1:p.Asp1692Asn missense NM_001407596.1:c.5074G>A NP_001394525.1:p.Asp1692Asn missense NM_001407597.1:c.5074G>A NP_001394526.1:p.Asp1692Asn missense NM_001407598.1:c.5074G>A NP_001394527.1:p.Asp1692Asn missense NM_001407602.1:c.5074G>A NP_001394531.1:p.Asp1692Asn missense NM_001407603.1:c.5074G>A NP_001394532.1:p.Asp1692Asn missense NM_001407605.1:c.5074G>A NP_001394534.1:p.Asp1692Asn missense NM_001407610.1:c.5071G>A NP_001394539.1:p.Asp1691Asn missense NM_001407611.1:c.5071G>A NP_001394540.1:p.Asp1691Asn missense NM_001407612.1:c.5071G>A NP_001394541.1:p.Asp1691Asn missense NM_001407613.1:c.5071G>A NP_001394542.1:p.Asp1691Asn missense NM_001407614.1:c.5071G>A NP_001394543.1:p.Asp1691Asn missense NM_001407615.1:c.5071G>A NP_001394544.1:p.Asp1691Asn missense NM_001407616.1:c.5071G>A NP_001394545.1:p.Asp1691Asn missense NM_001407617.1:c.5071G>A NP_001394546.1:p.Asp1691Asn missense NM_001407618.1:c.5071G>A NP_001394547.1:p.Asp1691Asn missense NM_001407619.1:c.5071G>A NP_001394548.1:p.Asp1691Asn missense NM_001407620.1:c.5071G>A NP_001394549.1:p.Asp1691Asn missense NM_001407621.1:c.5071G>A NP_001394550.1:p.Asp1691Asn missense NM_001407622.1:c.5071G>A NP_001394551.1:p.Asp1691Asn missense NM_001407623.1:c.5071G>A NP_001394552.1:p.Asp1691Asn missense NM_001407624.1:c.5071G>A NP_001394553.1:p.Asp1691Asn missense NM_001407625.1:c.5071G>A NP_001394554.1:p.Asp1691Asn missense NM_001407626.1:c.5071G>A NP_001394555.1:p.Asp1691Asn missense NM_001407627.1:c.5068G>A NP_001394556.1:p.Asp1690Asn missense NM_001407628.1:c.5068G>A NP_001394557.1:p.Asp1690Asn missense NM_001407629.1:c.5068G>A NP_001394558.1:p.Asp1690Asn missense NM_001407630.1:c.5068G>A NP_001394559.1:p.Asp1690Asn missense NM_001407631.1:c.5068G>A NP_001394560.1:p.Asp1690Asn missense NM_001407632.1:c.5068G>A NP_001394561.1:p.Asp1690Asn missense NM_001407633.1:c.5068G>A NP_001394562.1:p.Asp1690Asn missense NM_001407634.1:c.5068G>A NP_001394563.1:p.Asp1690Asn missense NM_001407635.1:c.5068G>A NP_001394564.1:p.Asp1690Asn missense NM_001407636.1:c.5068G>A NP_001394565.1:p.Asp1690Asn missense NM_001407637.1:c.5068G>A NP_001394566.1:p.Asp1690Asn missense NM_001407638.1:c.5068G>A NP_001394567.1:p.Asp1690Asn missense NM_001407639.1:c.5068G>A NP_001394568.1:p.Asp1690Asn missense NM_001407640.1:c.5068G>A NP_001394569.1:p.Asp1690Asn missense NM_001407641.1:c.5068G>A NP_001394570.1:p.Asp1690Asn missense NM_001407642.1:c.5068G>A NP_001394571.1:p.Asp1690Asn missense NM_001407644.1:c.5065G>A NP_001394573.1:p.Asp1689Asn missense NM_001407645.1:c.5065G>A NP_001394574.1:p.Asp1689Asn missense NM_001407646.1:c.5062G>A NP_001394575.1:p.Asp1688Asn missense NM_001407647.1:c.5059G>A NP_001394576.1:p.Asp1687Asn missense NM_001407648.1:c.5017G>A NP_001394577.1:p.Asp1673Asn missense NM_001407649.1:c.5014G>A NP_001394578.1:p.Asp1672Asn missense NM_001407652.1:c.5074G>A NP_001394581.1:p.Gly1692Arg missense NM_001407653.1:c.4996G>A NP_001394582.1:p.Asp1666Asn missense NM_001407654.1:c.4996G>A NP_001394583.1:p.Asp1666Asn missense NM_001407655.1:c.4996G>A NP_001394584.1:p.Asp1666Asn missense NM_001407656.1:c.4993G>A NP_001394585.1:p.Asp1665Asn missense NM_001407657.1:c.4993G>A NP_001394586.1:p.Asp1665Asn missense NM_001407658.1:c.4993G>A NP_001394587.1:p.Asp1665Asn missense NM_001407659.1:c.4990G>A NP_001394588.1:p.Asp1664Asn missense NM_001407660.1:c.4990G>A NP_001394589.1:p.Asp1664Asn missense NM_001407661.1:c.4990G>A NP_001394590.1:p.Asp1664Asn missense NM_001407662.1:c.4990G>A NP_001394591.1:p.Asp1664Asn missense NM_001407663.1:c.4990G>A NP_001394592.1:p.Asp1664Asn missense NM_001407664.1:c.4951G>A NP_001394593.1:p.Asp1651Asn missense NM_001407665.1:c.4951G>A NP_001394594.1:p.Asp1651Asn missense NM_001407666.1:c.4951G>A NP_001394595.1:p.Asp1651Asn missense NM_001407667.1:c.4951G>A NP_001394596.1:p.Asp1651Asn missense NM_001407668.1:c.4951G>A NP_001394597.1:p.Asp1651Asn missense NM_001407669.1:c.4951G>A NP_001394598.1:p.Asp1651Asn missense NM_001407670.1:c.4948G>A NP_001394599.1:p.Asp1650Asn missense NM_001407671.1:c.4948G>A NP_001394600.1:p.Asp1650Asn missense NM_001407672.1:c.4948G>A NP_001394601.1:p.Asp1650Asn missense NM_001407673.1:c.4948G>A NP_001394602.1:p.Asp1650Asn missense NM_001407674.1:c.4948G>A NP_001394603.1:p.Asp1650Asn missense NM_001407675.1:c.4948G>A NP_001394604.1:p.Asp1650Asn missense NM_001407676.1:c.4948G>A NP_001394605.1:p.Asp1650Asn missense NM_001407677.1:c.4948G>A NP_001394606.1:p.Asp1650Asn missense NM_001407678.1:c.4948G>A NP_001394607.1:p.Asp1650Asn missense NM_001407679.1:c.4948G>A NP_001394608.1:p.Asp1650Asn missense NM_001407680.1:c.4948G>A NP_001394609.1:p.Asp1650Asn missense NM_001407681.1:c.4945G>A NP_001394610.1:p.Asp1649Asn missense NM_001407682.1:c.4945G>A NP_001394611.1:p.Asp1649Asn missense NM_001407683.1:c.4945G>A NP_001394612.1:p.Asp1649Asn missense NM_001407684.1:c.5074G>A NP_001394613.1:p.Asp1692Asn missense NM_001407685.1:c.4945G>A NP_001394614.1:p.Asp1649Asn missense NM_001407686.1:c.4945G>A NP_001394615.1:p.Asp1649Asn missense NM_001407687.1:c.4945G>A NP_001394616.1:p.Asp1649Asn missense NM_001407688.1:c.4945G>A NP_001394617.1:p.Asp1649Asn missense NM_001407689.1:c.4945G>A NP_001394618.1:p.Asp1649Asn missense NM_001407690.1:c.4942G>A NP_001394619.1:p.Asp1648Asn missense NM_001407691.1:c.4942G>A NP_001394620.1:p.Asp1648Asn missense NM_001407692.1:c.4933G>A NP_001394621.1:p.Asp1645Asn missense NM_001407694.1:c.4933G>A NP_001394623.1:p.Asp1645Asn missense NM_001407695.1:c.4933G>A NP_001394624.1:p.Asp1645Asn missense NM_001407696.1:c.4933G>A NP_001394625.1:p.Asp1645Asn missense NM_001407697.1:c.4933G>A NP_001394626.1:p.Asp1645Asn missense NM_001407698.1:c.4933G>A NP_001394627.1:p.Asp1645Asn missense NM_001407724.1:c.4933G>A NP_001394653.1:p.Asp1645Asn missense NM_001407725.1:c.4933G>A NP_001394654.1:p.Asp1645Asn missense NM_001407726.1:c.4933G>A NP_001394655.1:p.Asp1645Asn missense NM_001407727.1:c.4933G>A NP_001394656.1:p.Asp1645Asn missense NM_001407728.1:c.4933G>A NP_001394657.1:p.Asp1645Asn missense NM_001407729.1:c.4933G>A NP_001394658.1:p.Asp1645Asn missense NM_001407730.1:c.4933G>A NP_001394659.1:p.Asp1645Asn missense NM_001407731.1:c.4933G>A NP_001394660.1:p.Asp1645Asn missense NM_001407732.1:c.4930G>A NP_001394661.1:p.Asp1644Asn missense NM_001407733.1:c.4930G>A NP_001394662.1:p.Asp1644Asn missense NM_001407734.1:c.4930G>A NP_001394663.1:p.Asp1644Asn missense NM_001407735.1:c.4930G>A NP_001394664.1:p.Asp1644Asn missense NM_001407736.1:c.4930G>A NP_001394665.1:p.Asp1644Asn missense NM_001407737.1:c.4930G>A NP_001394666.1:p.Asp1644Asn missense NM_001407738.1:c.4930G>A NP_001394667.1:p.Asp1644Asn missense NM_001407739.1:c.4930G>A NP_001394668.1:p.Asp1644Asn missense NM_001407740.1:c.4930G>A NP_001394669.1:p.Asp1644Asn missense NM_001407741.1:c.4930G>A NP_001394670.1:p.Asp1644Asn missense NM_001407742.1:c.4930G>A NP_001394671.1:p.Asp1644Asn missense NM_001407743.1:c.4930G>A NP_001394672.1:p.Asp1644Asn missense NM_001407744.1:c.4930G>A NP_001394673.1:p.Asp1644Asn missense NM_001407745.1:c.4930G>A NP_001394674.1:p.Asp1644Asn missense NM_001407746.1:c.4930G>A NP_001394675.1:p.Asp1644Asn missense NM_001407747.1:c.4930G>A NP_001394676.1:p.Asp1644Asn missense NM_001407748.1:c.4930G>A NP_001394677.1:p.Asp1644Asn missense NM_001407749.1:c.4930G>A NP_001394678.1:p.Asp1644Asn missense NM_001407750.1:c.4930G>A NP_001394679.1:p.Asp1644Asn missense NM_001407751.1:c.4930G>A NP_001394680.1:p.Asp1644Asn missense NM_001407752.1:c.4930G>A NP_001394681.1:p.Asp1644Asn missense NM_001407838.1:c.4927G>A NP_001394767.1:p.Asp1643Asn missense NM_001407839.1:c.4927G>A NP_001394768.1:p.Asp1643Asn missense NM_001407841.1:c.4927G>A NP_001394770.1:p.Asp1643Asn missense NM_001407842.1:c.4927G>A NP_001394771.1:p.Asp1643Asn missense NM_001407843.1:c.4927G>A NP_001394772.1:p.Asp1643Asn missense NM_001407844.1:c.4927G>A NP_001394773.1:p.Asp1643Asn missense NM_001407845.1:c.4927G>A NP_001394774.1:p.Asp1643Asn missense NM_001407846.1:c.4927G>A NP_001394775.1:p.Asp1643Asn missense NM_001407847.1:c.4927G>A NP_001394776.1:p.Asp1643Asn missense NM_001407848.1:c.4927G>A NP_001394777.1:p.Asp1643Asn missense NM_001407849.1:c.4927G>A NP_001394778.1:p.Asp1643Asn missense NM_001407850.1:c.4927G>A NP_001394779.1:p.Asp1643Asn missense NM_001407851.1:c.4927G>A NP_001394780.1:p.Asp1643Asn missense NM_001407852.1:c.4927G>A NP_001394781.1:p.Asp1643Asn missense NM_001407853.1:c.4927G>A NP_001394782.1:p.Asp1643Asn missense NM_001407854.1:c.5074G>A NP_001394783.1:p.Asp1692Asn missense NM_001407858.1:c.5071G>A NP_001394787.1:p.Asp1691Asn missense NM_001407859.1:c.5071G>A NP_001394788.1:p.Asp1691Asn missense NM_001407860.1:c.5071G>A NP_001394789.1:p.Asp1691Asn missense NM_001407861.1:c.5068G>A NP_001394790.1:p.Asp1690Asn missense NM_001407862.1:c.4873G>A NP_001394791.1:p.Asp1625Asn missense NM_001407863.1:c.4948G>A NP_001394792.1:p.Gly1650Arg missense NM_001407874.1:c.4867G>A NP_001394803.1:p.Asp1623Asn missense NM_001407875.1:c.4867G>A NP_001394804.1:p.Asp1623Asn missense NM_001407879.1:c.4864G>A NP_001394808.1:p.Asp1622Asn missense NM_001407881.1:c.4864G>A NP_001394810.1:p.Asp1622Asn missense NM_001407882.1:c.4864G>A NP_001394811.1:p.Asp1622Asn missense NM_001407884.1:c.4864G>A NP_001394813.1:p.Asp1622Asn missense NM_001407885.1:c.4864G>A NP_001394814.1:p.Asp1622Asn missense NM_001407886.1:c.4864G>A NP_001394815.1:p.Asp1622Asn missense NM_001407887.1:c.4864G>A NP_001394816.1:p.Asp1622Asn missense NM_001407889.1:c.4864G>A NP_001394818.1:p.Asp1622Asn missense NM_001407894.1:c.4861G>A NP_001394823.1:p.Asp1621Asn missense NM_001407895.1:c.4861G>A NP_001394824.1:p.Asp1621Asn missense NM_001407896.1:c.4861G>A NP_001394825.1:p.Asp1621Asn missense NM_001407897.1:c.4861G>A NP_001394826.1:p.Asp1621Asn missense NM_001407898.1:c.4861G>A NP_001394827.1:p.Asp1621Asn missense NM_001407899.1:c.4861G>A NP_001394828.1:p.Asp1621Asn missense NM_001407900.1:c.4861G>A NP_001394829.1:p.Asp1621Asn missense NM_001407902.1:c.4861G>A NP_001394831.1:p.Asp1621Asn missense NM_001407904.1:c.4861G>A NP_001394833.1:p.Asp1621Asn missense NM_001407906.1:c.4861G>A NP_001394835.1:p.Asp1621Asn missense NM_001407907.1:c.4861G>A NP_001394836.1:p.Asp1621Asn missense NM_001407908.1:c.4861G>A NP_001394837.1:p.Asp1621Asn missense NM_001407909.1:c.4861G>A NP_001394838.1:p.Asp1621Asn missense NM_001407910.1:c.4861G>A NP_001394839.1:p.Asp1621Asn missense NM_001407915.1:c.4858G>A NP_001394844.1:p.Asp1620Asn missense NM_001407916.1:c.4858G>A NP_001394845.1:p.Asp1620Asn missense NM_001407917.1:c.4858G>A NP_001394846.1:p.Asp1620Asn missense NM_001407918.1:c.4858G>A NP_001394847.1:p.Asp1620Asn missense NM_001407919.1:c.4951G>A NP_001394848.1:p.Asp1651Asn missense NM_001407920.1:c.4810G>A NP_001394849.1:p.Asp1604Asn missense NM_001407921.1:c.4810G>A NP_001394850.1:p.Asp1604Asn missense NM_001407922.1:c.4810G>A NP_001394851.1:p.Asp1604Asn missense NM_001407923.1:c.4810G>A NP_001394852.1:p.Asp1604Asn missense NM_001407924.1:c.4810G>A NP_001394853.1:p.Asp1604Asn missense NM_001407925.1:c.4810G>A NP_001394854.1:p.Asp1604Asn missense NM_001407926.1:c.4810G>A NP_001394855.1:p.Asp1604Asn missense NM_001407927.1:c.4807G>A NP_001394856.1:p.Asp1603Asn missense NM_001407928.1:c.4807G>A NP_001394857.1:p.Asp1603Asn missense NM_001407929.1:c.4807G>A NP_001394858.1:p.Asp1603Asn missense NM_001407930.1:c.4807G>A NP_001394859.1:p.Asp1603Asn missense NM_001407931.1:c.4807G>A NP_001394860.1:p.Asp1603Asn missense NM_001407932.1:c.4807G>A NP_001394861.1:p.Asp1603Asn missense NM_001407933.1:c.4807G>A NP_001394862.1:p.Asp1603Asn missense NM_001407934.1:c.4804G>A NP_001394863.1:p.Asp1602Asn missense NM_001407935.1:c.4804G>A NP_001394864.1:p.Asp1602Asn missense NM_001407936.1:c.4804G>A NP_001394865.1:p.Asp1602Asn missense NM_001407937.1:c.4951G>A NP_001394866.1:p.Asp1651Asn missense NM_001407938.1:c.4951G>A NP_001394867.1:p.Asp1651Asn missense NM_001407939.1:c.4948G>A NP_001394868.1:p.Asp1650Asn missense NM_001407940.1:c.4948G>A NP_001394869.1:p.Asp1650Asn missense NM_001407941.1:c.4945G>A NP_001394870.1:p.Asp1649Asn missense NM_001407942.1:c.4933G>A NP_001394871.1:p.Asp1645Asn missense NM_001407943.1:c.4930G>A NP_001394872.1:p.Asp1644Asn missense NM_001407944.1:c.4930G>A NP_001394873.1:p.Asp1644Asn missense NM_001407945.1:c.4930G>A NP_001394874.1:p.Asp1644Asn missense NM_001407946.1:c.4741G>A NP_001394875.1:p.Asp1581Asn missense NM_001407947.1:c.4741G>A NP_001394876.1:p.Asp1581Asn missense NM_001407948.1:c.4741G>A NP_001394877.1:p.Asp1581Asn missense NM_001407949.1:c.4741G>A NP_001394878.1:p.Asp1581Asn missense NM_001407950.1:c.4738G>A NP_001394879.1:p.Asp1580Asn missense NM_001407951.1:c.4738G>A NP_001394880.1:p.Asp1580Asn missense NM_001407952.1:c.4738G>A NP_001394881.1:p.Asp1580Asn missense NM_001407953.1:c.4738G>A NP_001394882.1:p.Asp1580Asn missense NM_001407954.1:c.4738G>A NP_001394883.1:p.Asp1580Asn missense NM_001407955.1:c.4738G>A NP_001394884.1:p.Asp1580Asn missense NM_001407956.1:c.4735G>A NP_001394885.1:p.Asp1579Asn missense NM_001407957.1:c.4735G>A NP_001394886.1:p.Asp1579Asn missense NM_001407958.1:c.4735G>A NP_001394887.1:p.Asp1579Asn missense NM_001407959.1:c.4693G>A NP_001394888.1:p.Asp1565Asn missense NM_001407960.1:c.4690G>A NP_001394889.1:p.Asp1564Asn missense NM_001407962.1:c.4690G>A NP_001394891.1:p.Asp1564Asn missense NM_001407963.1:c.4687G>A NP_001394892.1:p.Asp1563Asn missense NM_001407964.1:c.4612G>A NP_001394893.1:p.Asp1538Asn missense NM_001407965.1:c.4567G>A NP_001394894.1:p.Asp1523Asn missense NM_001407966.1:c.4186G>A NP_001394895.1:p.Asp1396Asn missense NM_001407967.1:c.4183G>A NP_001394896.1:p.Asp1395Asn missense NM_001407968.1:c.2470G>A NP_001394897.1:p.Asp824Asn missense NM_001407969.1:c.2467G>A NP_001394898.1:p.Asp823Asn missense NM_001407970.1:c.1831G>A NP_001394899.1:p.Asp611Asn missense NM_001407971.1:c.1831G>A NP_001394900.1:p.Asp611Asn missense NM_001407972.1:c.1828G>A NP_001394901.1:p.Asp610Asn missense NM_001407973.1:c.1765G>A NP_001394902.1:p.Asp589Asn missense NM_001407974.1:c.1765G>A NP_001394903.1:p.Asp589Asn missense NM_001407975.1:c.1765G>A NP_001394904.1:p.Asp589Asn missense NM_001407976.1:c.1765G>A NP_001394905.1:p.Asp589Asn missense NM_001407977.1:c.1765G>A NP_001394906.1:p.Asp589Asn missense NM_001407978.1:c.1765G>A NP_001394907.1:p.Asp589Asn missense NM_001407979.1:c.1762G>A NP_001394908.1:p.Asp588Asn missense NM_001407980.1:c.1762G>A NP_001394909.1:p.Asp588Asn missense NM_001407981.1:c.1762G>A NP_001394910.1:p.Asp588Asn missense NM_001407982.1:c.1762G>A NP_001394911.1:p.Asp588Asn missense NM_001407983.1:c.1762G>A NP_001394912.1:p.Asp588Asn missense NM_001407984.1:c.1762G>A NP_001394913.1:p.Asp588Asn missense NM_001407985.1:c.1762G>A NP_001394914.1:p.Asp588Asn missense NM_001407986.1:c.1762G>A NP_001394915.1:p.Asp588Asn missense NM_001407990.1:c.1762G>A NP_001394919.1:p.Asp588Asn missense NM_001407991.1:c.1762G>A NP_001394920.1:p.Asp588Asn missense NM_001407992.1:c.1762G>A NP_001394921.1:p.Asp588Asn missense NM_001407993.1:c.1762G>A NP_001394922.1:p.Asp588Asn missense NM_001408392.1:c.1759G>A NP_001395321.1:p.Asp587Asn missense NM_001408396.1:c.1759G>A NP_001395325.1:p.Asp587Asn missense NM_001408397.1:c.1759G>A NP_001395326.1:p.Asp587Asn missense NM_001408398.1:c.1759G>A NP_001395327.1:p.Asp587Asn missense NM_001408399.1:c.1759G>A NP_001395328.1:p.Asp587Asn missense NM_001408400.1:c.1759G>A NP_001395329.1:p.Asp587Asn missense NM_001408401.1:c.1759G>A NP_001395330.1:p.Asp587Asn missense NM_001408402.1:c.1759G>A NP_001395331.1:p.Asp587Asn missense NM_001408403.1:c.1759G>A NP_001395332.1:p.Asp587Asn missense NM_001408404.1:c.1759G>A NP_001395333.1:p.Asp587Asn missense NM_001408406.1:c.1756G>A NP_001395335.1:p.Asp586Asn missense NM_001408407.1:c.1756G>A NP_001395336.1:p.Asp586Asn missense NM_001408408.1:c.1756G>A NP_001395337.1:p.Asp586Asn missense NM_001408409.1:c.1753G>A NP_001395338.1:p.Asp585Asn missense NM_001408410.1:c.1690G>A NP_001395339.1:p.Asp564Asn missense NM_001408411.1:c.1687G>A NP_001395340.1:p.Asp563Asn missense NM_001408412.1:c.1684G>A NP_001395341.1:p.Asp562Asn missense NM_001408413.1:c.1684G>A NP_001395342.1:p.Asp562Asn missense NM_001408414.1:c.1684G>A NP_001395343.1:p.Asp562Asn missense NM_001408415.1:c.1684G>A NP_001395344.1:p.Asp562Asn missense NM_001408416.1:c.1684G>A NP_001395345.1:p.Asp562Asn missense NM_001408418.1:c.1648G>A NP_001395347.1:p.Asp550Asn missense NM_001408419.1:c.1648G>A NP_001395348.1:p.Asp550Asn missense NM_001408420.1:c.1648G>A NP_001395349.1:p.Asp550Asn missense NM_001408421.1:c.1645G>A NP_001395350.1:p.Asp549Asn missense NM_001408422.1:c.1645G>A NP_001395351.1:p.Asp549Asn missense NM_001408423.1:c.1645G>A NP_001395352.1:p.Asp549Asn missense NM_001408424.1:c.1645G>A NP_001395353.1:p.Asp549Asn missense NM_001408425.1:c.1642G>A NP_001395354.1:p.Asp548Asn missense NM_001408426.1:c.1642G>A NP_001395355.1:p.Asp548Asn missense NM_001408427.1:c.1642G>A NP_001395356.1:p.Asp548Asn missense NM_001408428.1:c.1642G>A NP_001395357.1:p.Asp548Asn missense NM_001408429.1:c.1642G>A NP_001395358.1:p.Asp548Asn missense NM_001408430.1:c.1642G>A NP_001395359.1:p.Asp548Asn missense NM_001408431.1:c.1642G>A NP_001395360.1:p.Asp548Asn missense NM_001408432.1:c.1639G>A NP_001395361.1:p.Asp547Asn missense NM_001408433.1:c.1639G>A NP_001395362.1:p.Asp547Asn missense NM_001408434.1:c.1639G>A NP_001395363.1:p.Asp547Asn missense NM_001408435.1:c.1639G>A NP_001395364.1:p.Asp547Asn missense NM_001408436.1:c.1639G>A NP_001395365.1:p.Asp547Asn missense NM_001408437.1:c.1639G>A NP_001395366.1:p.Asp547Asn missense NM_001408438.1:c.1639G>A NP_001395367.1:p.Asp547Asn missense NM_001408439.1:c.1639G>A NP_001395368.1:p.Asp547Asn missense NM_001408440.1:c.1639G>A NP_001395369.1:p.Asp547Asn missense NM_001408441.1:c.1639G>A NP_001395370.1:p.Asp547Asn missense NM_001408442.1:c.1639G>A NP_001395371.1:p.Asp547Asn missense NM_001408443.1:c.1639G>A NP_001395372.1:p.Asp547Asn missense NM_001408444.1:c.1639G>A NP_001395373.1:p.Asp547Asn missense NM_001408445.1:c.1636G>A NP_001395374.1:p.Asp546Asn missense NM_001408446.1:c.1636G>A NP_001395375.1:p.Asp546Asn missense NM_001408447.1:c.1636G>A NP_001395376.1:p.Asp546Asn missense NM_001408448.1:c.1636G>A NP_001395377.1:p.Asp546Asn missense NM_001408450.1:c.1636G>A NP_001395379.1:p.Asp546Asn missense NM_001408451.1:c.1630G>A NP_001395380.1:p.Asp544Asn missense NM_001408452.1:c.1624G>A NP_001395381.1:p.Asp542Asn missense NM_001408453.1:c.1624G>A NP_001395382.1:p.Asp542Asn missense NM_001408454.1:c.1624G>A NP_001395383.1:p.Asp542Asn missense NM_001408455.1:c.1624G>A NP_001395384.1:p.Asp542Asn missense NM_001408456.1:c.1624G>A NP_001395385.1:p.Asp542Asn missense NM_001408457.1:c.1624G>A NP_001395386.1:p.Asp542Asn missense NM_001408458.1:c.1621G>A NP_001395387.1:p.Asp541Asn missense NM_001408459.1:c.1621G>A NP_001395388.1:p.Asp541Asn missense NM_001408460.1:c.1621G>A NP_001395389.1:p.Asp541Asn missense NM_001408461.1:c.1621G>A NP_001395390.1:p.Asp541Asn missense NM_001408462.1:c.1621G>A NP_001395391.1:p.Asp541Asn missense NM_001408463.1:c.1621G>A NP_001395392.1:p.Asp541Asn missense NM_001408464.1:c.1621G>A NP_001395393.1:p.Asp541Asn missense NM_001408465.1:c.1621G>A NP_001395394.1:p.Asp541Asn missense NM_001408466.1:c.1621G>A NP_001395395.1:p.Asp541Asn missense NM_001408467.1:c.1621G>A NP_001395396.1:p.Asp541Asn missense NM_001408468.1:c.1618G>A NP_001395397.1:p.Asp540Asn missense NM_001408469.1:c.1618G>A NP_001395398.1:p.Asp540Asn missense NM_001408470.1:c.1618G>A NP_001395399.1:p.Asp540Asn missense NM_001408472.1:c.1762G>A NP_001395401.1:p.Asp588Asn missense NM_001408473.1:c.1759G>A NP_001395402.1:p.Asp587Asn missense NM_001408474.1:c.1564G>A NP_001395403.1:p.Asp522Asn missense NM_001408475.1:c.1561G>A NP_001395404.1:p.Asp521Asn missense NM_001408476.1:c.1561G>A NP_001395405.1:p.Asp521Asn missense NM_001408478.1:c.1555G>A NP_001395407.1:p.Asp519Asn missense NM_001408479.1:c.1555G>A NP_001395408.1:p.Asp519Asn missense NM_001408480.1:c.1555G>A NP_001395409.1:p.Asp519Asn missense NM_001408481.1:c.1552G>A NP_001395410.1:p.Asp518Asn missense NM_001408482.1:c.1552G>A NP_001395411.1:p.Asp518Asn missense NM_001408483.1:c.1552G>A NP_001395412.1:p.Asp518Asn missense NM_001408484.1:c.1552G>A NP_001395413.1:p.Asp518Asn missense NM_001408485.1:c.1552G>A NP_001395414.1:p.Asp518Asn missense NM_001408489.1:c.1552G>A NP_001395418.1:p.Asp518Asn missense NM_001408490.1:c.1552G>A NP_001395419.1:p.Asp518Asn missense NM_001408491.1:c.1552G>A NP_001395420.1:p.Asp518Asn missense NM_001408492.1:c.1549G>A NP_001395421.1:p.Asp517Asn missense NM_001408493.1:c.1549G>A NP_001395422.1:p.Asp517Asn missense NM_001408494.1:c.1525G>A NP_001395423.1:p.Asp509Asn missense NM_001408495.1:c.1519G>A NP_001395424.1:p.Asp507Asn missense NM_001408496.1:c.1501G>A NP_001395425.1:p.Asp501Asn missense NM_001408497.1:c.1501G>A NP_001395426.1:p.Asp501Asn missense NM_001408498.1:c.1501G>A NP_001395427.1:p.Asp501Asn missense NM_001408499.1:c.1501G>A NP_001395428.1:p.Asp501Asn missense NM_001408500.1:c.1501G>A NP_001395429.1:p.Asp501Asn missense NM_001408501.1:c.1501G>A NP_001395430.1:p.Asp501Asn missense NM_001408502.1:c.1498G>A NP_001395431.1:p.Asp500Asn missense NM_001408503.1:c.1498G>A NP_001395432.1:p.Asp500Asn missense NM_001408504.1:c.1498G>A NP_001395433.1:p.Asp500Asn missense NM_001408505.1:c.1495G>A NP_001395434.1:p.Asp499Asn missense NM_001408506.1:c.1438G>A NP_001395435.1:p.Asp480Asn missense NM_001408507.1:c.1435G>A NP_001395436.1:p.Asp479Asn missense NM_001408508.1:c.1426G>A NP_001395437.1:p.Asp476Asn missense NM_001408509.1:c.1423G>A NP_001395438.1:p.Asp475Asn missense NM_001408510.1:c.1384G>A NP_001395439.1:p.Asp462Asn missense NM_001408511.1:c.1381G>A NP_001395440.1:p.Asp461Asn missense NM_001408512.1:c.1261G>A NP_001395441.1:p.Asp421Asn missense NM_001408513.1:c.1234G>A NP_001395442.1:p.Asp412Asn missense NM_007297.4:c.4933G>A NP_009228.2:p.Asp1645Asn missense NM_007298.4:c.1762G>A NP_009229.2:p.Asp588Asn missense NM_007299.4:c.1762G>A NP_009230.2:p.Asp588Asn missense NM_007300.4:c.5137G>A NP_009231.2:p.Asp1713Asn missense NM_007304.2:c.1762G>A NP_009235.2:p.Asp588Asn missense NR_027676.2:n.5251G>A non-coding transcript variant NC_000017.11:g.43067608C>T NC_000017.10:g.41219625C>T NG_005905.2:g.150376G>A LRG_292:g.150376G>A LRG_292t1:c.5074G>A LRG_292p1:p.Asp1692Asn U14680.1:n.5193G>A - Protein change
- D1692N, D1645N, D1713N, D588N, D1620N, D1648N, D1649N, D1650N, D1665N, D412N, D421N, D462N, D479N, D521N, D541N, D542N, D544N, D546N, D547N, D563N, D586N, D611N, D1523N, D1564N, D1565N, D1581N, D1603N, D1623N, D1673N, D1689N, D1691N, D500N, D519N, D540N, D549N, D550N, D562N, D564N, D587N, D823N, G1692R, D1395N, D1563N, D1579N, D1602N, D1622N, D1651N, D1664N, D1666N, D1687N, D1712N, D475N, D499N, D509N, D517N, D548N, D585N, G1650R, D1396N, D1538N, D1580N, D1604N, D1621N, D1625N, D1643N, D1644N, D1672N, D1688N, D1690N, D1714N, D461N, D476N, D480N, D501N, D507N, D518N, D522N, D589N, D610N, D824N
- Other names
-
5193G>A
- Canonical SPDI
- NC_000017.11:43067607:C:T
-
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.5074G>A, a MISSENSE variant, produced a function score of -1.86, 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.
- -
- 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 |
13470 | 15363 | |
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/Likely pathogenic (8) |
criteria provided, multiple submitters, no conflicts
|
Nov 4, 2022 | RCV000031213.26 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Nov 21, 2020 | RCV000217586.15 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Mar 4, 2025 | RCV000255870.12 | |
| Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Oct 16, 2024 | RCV000496924.16 | |
| Pathogenic (1) |
no assertion criteria provided
|
- | RCV003332088.2 |
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
(Nov 04, 2022)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: unknown
Allele origin:
germline
|
St. Jude Molecular Pathology, St. Jude Children's Research Hospital
Accession: SCV003843144.2
First in ClinVar: Mar 26, 2023 Last updated: Apr 15, 2024 |
Comment:
The BRCA1 c.5074G>A (p.Asp1692Asn) missense change affects the last nucleotide of exon 16 and is predicted to abolish the native splice donor site. An in … (more)
The BRCA1 c.5074G>A (p.Asp1692Asn) missense change affects the last nucleotide of exon 16 and is predicted to abolish the native splice donor site. An in vitro study demonstrated that this variant leads to multiple aberrant transcripts, including one causing exon 17 skipping and another causing activation of a cryptic splice donor site that leads to an in-frame retention of 153 bp of intron 17 (PMID: 25724305). These published findings are also supported by internal data. This variant has been reported in individuals with a personal and/or family history of breast and/or ovarian cancer (PMID: 8460636, 9452084, 10196379, 15571962). It is commonly reported in individuals of Icelandic ancestry and genetic linkage analysis suggests that this is an Icelandic founder mutation (PMID: 8460636, 9452084, 15571962). It is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as likely pathogenic. (less)
|
|
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Pathogenic
(May 20, 2022)
C
Contributing to aggregate classification
|
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: SCV002578917.2
First in ClinVar: Oct 15, 2022 Last updated: Apr 13, 2025
Comment:
ACMG criteria applied: PS3, PS4, PM5, PM2_SUP, PP1
|
Number of individuals with the variant: 1
Sex: female
|
|
|
Pathogenic
(Mar 11, 2020)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000904696.3
First in ClinVar: May 20, 2019 Last updated: Jan 15, 2022 |
Comment:
This missense variant replaces aspartic acid with asparagine at codon 1692 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant … (more)
This missense variant replaces aspartic acid with asparagine at codon 1692 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. Functional RNA studies have shown that this variant causes a splicing defect leading to skipping of exon 16 or in-frame retention of part of intron 15 (PMID: 25724305). This variant has been reported in individuals affected with familial breast/ovarian cancer (PMID: 9452084, 10196379, 11157798, 15571962). This variant has not been identified 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)
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|
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Pathogenic
(Oct 02, 2015)
C
Contributing to aggregate classification
|
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: SCV000326135.4
First in ClinVar: May 27, 2015 Last updated: Dec 11, 2022 |
|
|
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Pathogenic
(Mar 30, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003923014.1
First in ClinVar: May 13, 2023 Last updated: May 13, 2023 |
Comment:
Variant summary: BRCA1 c.5074G>A (p.Asp1692Asn) results in a conservative amino acid change located in the BRCT domain of the encoded protein sequence. Three of five … (more)
Variant summary: BRCA1 c.5074G>A (p.Asp1692Asn) results in a conservative amino acid change located in the BRCT domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251348 control chromosomes. c.5074G>A has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome. In families with this variant, 11 transmissions of the variant allele and 1 transmissions of the reference allele to affected individuals was reported. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function and showed that this variant results in loss of function (Findlay_2018). Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (pathogenic/likely pathogenic n=7, VUS n=1). Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Jul 27, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000322096.8
First in ClinVar: Oct 09, 2016 Last updated: Aug 05, 2023 |
Comment:
Alters the last nucleotide of the exon and demonstrated to cause aberrant splicing, resulting predominantly in out-of-frame skipping of exon 17, as well as use … (more)
Alters the last nucleotide of the exon and demonstrated to cause aberrant splicing, resulting predominantly in out-of-frame skipping of exon 17, as well as use of a cryptic splice donor site (Ahlborn et al., 2015); Described as an Icelandic founder variant which has been observed in individuals with breast or ovarian cancer (Arason et al., 1998; Bergthorsson et al., 1998; Janezic et al., 1999; Rafnar et al., 2004; Carter et al., 2018; Li et al., 2018; Zheng et al., 2018; Su et al., 2021); Published functional studies demonstrate a damaging effect: classified as non-functional based on a saturation genome editing (SGE) assay measuring cell growth (Findlay et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); Also known as 5193G>A; This variant is associated with the following publications: (PMID: 25722380, 30251169, 15235020, 25724305, 9452084, 20378548, 11157798, 20516115, 15571962, 15172985, 17305420, 23239986, 25748678, 24772314, 10196379, 27495310, 21447777, 16267036, 28726806, 29446198, 23199084, 21769658, 21147198, 12531920, 30078507, 30322717, 9500438, 29996917, 29884841, 32546644, 35665744, 32211327, 30130155, 9643283, 34917121, 36068545, 35171259, 25348405, 30209399) (less)
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Pathogenic
(Nov 21, 2020)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000273244.5
First in ClinVar: May 29, 2016 Last updated: May 01, 2024 |
Comment:
The c.5074G>A variant (also known as p.D1692N), located in coding exon 15 of the BRCA1 gene, results from a G to A substitution at nucleotide … (more)
The c.5074G>A variant (also known as p.D1692N), located in coding exon 15 of the BRCA1 gene, results from a G to A substitution at nucleotide position 5074. The amino acid change results in aspartic acid to asparagine at codon 1692, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 15, which makes it likely to have some effect on normal mRNA splicing. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Minigene RNA analysis shows that this variant results in the skipping of exon 17 and to use a cryptic splice donor site 153 base pairs of the 5' end of intron 17, the aberrant effect of which is also observed in a haploid cell survival assay (Ahlborn LB, et al. Breast Cancer Res.Treat. 2015;150(2):289-98; Findlay GM. Nature. 2018 10;562(7726):217-222). This alteration segregated with disease in a large family and is considered an Icelandic founder mutation (Bergthorsson JT, et al. Hum. Mutat. 1998 ; Suppl 1():S195-7). Functional and computational analyses of this variant at the protein level largely reflect the missense change to be tolerated (Abkevich V, et al. J. Med. Genet. 2004;41(7):492-507; Rowling PJ, et al. J. Biol. Chem. 2010;285(26):20080-7; Lee MS, et al. Cancer Res. 2010;70(12):4880-90; Vallon-Christersson J, et al. Hum. Mol. Genet. 2001;10(4):353-60; Bouwman P et al. Clin Cancer Res, 2020 Sep;26:4559-4568; Gaboriau DC et al. Biochem J, 2015 Mar;466:613-24). Of note, this alteration is also designated as 5193G>A in published literature. The nucleotide and amino acid positions are highly conserved in available vertebrate species. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
|
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Pathogenic
(Oct 16, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001585898.5
First in ClinVar: May 10, 2021 Last updated: Feb 25, 2025 |
Comment:
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1692 of the BRCA1 protein … (more)
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1692 of the BRCA1 protein (p.Asp1692Asn). This variant also falls at the last nucleotide of exon 16, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 8460636, 9452084, 10196379, 15571962). It is commonly reported in individuals of Icelandic ancestry (PMID: 8460636, 9452084, 15571962). This variant is also known as 5193G>A. ClinVar contains an entry for this variant (Variation ID: 37632). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 25748678, 30209399). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. (less)
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|
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Pathogenic
(Mar 04, 2025)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV005872176.1
First in ClinVar: Mar 11, 2025 Last updated: Mar 11, 2025 |
|
|
|
Likely pathogenic
(Jul 25, 2006)
N
Not contributing to aggregate classification
|
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: SCV000053813.5
First in ClinVar: Apr 04, 2013 Last updated: May 27, 2015 |
|
|
|
Likely pathogenic
(Dec 17, 2015)
N
Not contributing to aggregate classification
|
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: SCV000587454.1 First in ClinVar: Aug 07, 2017 Last updated: Aug 07, 2017 |
|
|
|
Pathogenic
(Jul 21, 2023)
N
Not contributing to aggregate classification
|
no assertion criteria provided
Method: research
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
deCODE genetics, Amgen
Accession: SCV004022171.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
Comment:
The variant NM_007294.4:c.5074G>A (chr17:43067608) in BRCA1 was detected in 26 heterozygotes out of 58K WGS Icelanders (MAF= 0,022%). Following imputation in a set of 166K … (more)
The variant NM_007294.4:c.5074G>A (chr17:43067608) in BRCA1 was detected in 26 heterozygotes out of 58K WGS Icelanders (MAF= 0,022%). Following imputation in a set of 166K Icelanders (70 imputed heterozygotes) we observed an association with breast cancer using 6908 cases and 292623 controls (OR= 20.57, P= 8.44e-16) and ovarian cancer using 907 cases and 299709 controls (OR= 29.05, P= 2.67e-10). This variant has been reported in ClinVar previously as pathogenic/likely pathogenic. Based on ACMG criteria (PS4, PP1, PP3, PP5_Strong) this variant classifies as pathogenic. (less)
Number of individuals with the variant: 70
Ethnicity/Population group: Icelandic
|
|
|
Likely pathogenic
(Sep 01, 2023)
N
Not contributing to aggregate classification
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 1
Affected status: yes
Allele origin:
germline
|
Department of Medical and Surgical Sciences, University of Bologna
Accession: SCV004228368.1
First in ClinVar: Jan 26, 2024 Last updated: Jan 26, 2024 |
Comment:
PS3(Strong)+PM2(Supporting)+PP3(Supporting)+PP4(Supporting) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)
|
|
|
Pathogenic
(May 29, 2002)
N
Not contributing to aggregate classification
|
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: SCV000145293.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 6
Observation 2:
Number of individuals with the variant: 1
Ethnicity/Population group: African
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: African American
Observation 4:
Number of individuals with the variant: 1
Ethnicity/Population group: Latin American, Caribbean
Observation 5:
Number of individuals with the variant: 2
Ethnicity/Population group: Western European
|
|
|
Pathogenic
(-)
N
Not contributing to aggregate classification
|
no assertion criteria provided
Method: research
|
Malignant tumor of urinary bladder
Affected status: yes
Allele origin:
somatic
|
Laboratory of Urology, Hospital Clinic de Barcelona
Accession: SCV004040520.1
First in ClinVar: Oct 07, 2023 Last updated: Oct 07, 2023 |
|
|
|
not provided
(-)
N
Not contributing to aggregate classification
|
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: SCV001244020.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
Method: saturation genome editing in haploid cells
Result:
LOSS_OF_FUNCTION:-1.86484269773559
|
|
| click to load more submissions click to collapse | |||||
Comment:
Comment:
This missense variant replaces aspartic acid with asparagine at codon 1692 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. Functional RNA studies have shown that this variant causes a splicing defect leading to skipping of exon 16 or in-frame retention of part of intron 15 (PMID: 25724305). This variant has been reported in individuals affected with familial breast/ovarian cancer (PMID: 9452084, 10196379, 11157798, 15571962). This variant has not been identified 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:
Variant summary: BRCA1 c.5074G>A (p.Asp1692Asn) results in a conservative amino acid change located in the BRCT domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251348 control chromosomes. c.5074G>A has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome. In families with this variant, 11 transmissions of the variant allele and 1 transmissions of the reference allele to affected individuals was reported. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function and showed that this variant results in loss of function (Findlay_2018). Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (pathogenic/likely pathogenic n=7, VUS n=1). Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
Alters the last nucleotide of the exon and demonstrated to cause aberrant splicing, resulting predominantly in out-of-frame skipping of exon 17, as well as use of a cryptic splice donor site (Ahlborn et al., 2015); Described as an Icelandic founder variant which has been observed in individuals with breast or ovarian cancer (Arason et al., 1998; Bergthorsson et al., 1998; Janezic et al., 1999; Rafnar et al., 2004; Carter et al., 2018; Li et al., 2018; Zheng et al., 2018; Su et al., 2021); Published functional studies demonstrate a damaging effect: classified as non-functional based on a saturation genome editing (SGE) assay measuring cell growth (Findlay et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); Also known as 5193G>A; This variant is associated with the following publications: (PMID: 25722380, 30251169, 15235020, 25724305, 9452084, 20378548, 11157798, 20516115, 15571962, 15172985, 17305420, 23239986, 25748678, 24772314, 10196379, 27495310, 21447777, 16267036, 28726806, 29446198, 23199084, 21769658, 21147198, 12531920, 30078507, 30322717, 9500438, 29996917, 29884841, 32546644, 35665744, 32211327, 30130155, 9643283, 34917121, 36068545, 35171259, 25348405, 30209399)
Comment:
The c.5074G>A variant (also known as p.D1692N), located in coding exon 15 of the BRCA1 gene, results from a G to A substitution at nucleotide position 5074. The amino acid change results in aspartic acid to asparagine at codon 1692, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 15, which makes it likely to have some effect on normal mRNA splicing. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Minigene RNA analysis shows that this variant results in the skipping of exon 17 and to use a cryptic splice donor site 153 base pairs of the 5' end of intron 17, the aberrant effect of which is also observed in a haploid cell survival assay (Ahlborn LB, et al. Breast Cancer Res.Treat. 2015;150(2):289-98; Findlay GM. Nature. 2018 10;562(7726):217-222). This alteration segregated with disease in a large family and is considered an Icelandic founder mutation (Bergthorsson JT, et al. Hum. Mutat. 1998 ; Suppl 1():S195-7). Functional and computational analyses of this variant at the protein level largely reflect the missense change to be tolerated (Abkevich V, et al. J. Med. Genet. 2004;41(7):492-507; Rowling PJ, et al. J. Biol. Chem. 2010;285(26):20080-7; Lee MS, et al. Cancer Res. 2010;70(12):4880-90; Vallon-Christersson J, et al. Hum. Mol. Genet. 2001;10(4):353-60; Bouwman P et al. Clin Cancer Res, 2020 Sep;26:4559-4568; Gaboriau DC et al. Biochem J, 2015 Mar;466:613-24). Of note, this alteration is also designated as 5193G>A in published literature. The nucleotide and amino acid positions are highly conserved in available vertebrate species. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Comment:
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1692 of the BRCA1 protein (p.Asp1692Asn). This variant also falls at the last nucleotide of exon 16, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 8460636, 9452084, 10196379, 15571962). It is commonly reported in individuals of Icelandic ancestry (PMID: 8460636, 9452084, 15571962). This variant is also known as 5193G>A. ClinVar contains an entry for this variant (Variation ID: 37632). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 25748678, 30209399). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Comment:
The variant NM_007294.4:c.5074G>A (chr17:43067608) in BRCA1 was detected in 26 heterozygotes out of 58K WGS Icelanders (MAF= 0,022%). Following imputation in a set of 166K Icelanders (70 imputed heterozygotes) we observed an association with breast cancer using 6908 cases and 292623 controls (OR= 20.57, P= 8.44e-16) and ovarian cancer using 907 cases and 299709 controls (OR= 29.05, P= 2.67e-10). This variant has been reported in ClinVar previously as pathogenic/likely pathogenic. Based on ACMG criteria (PS4, PP1, PP3, PP5_Strong) this variant classifies as pathogenic.
Comment:
PS3(Strong)+PM2(Supporting)+PP3(Supporting)+PP4(Supporting) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)
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_abnormal
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Method citation(s):
|
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Brotman Baty Institute, University of Washington
Accession: SCV001244020.1
|
Comment:
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5074G>A, a MISSENSE variant, produced a function score of -1.86, corresponding to a functional classification of LOSS_OF_FUNCTION. … (more)
The saturation genome editing (SGE) assay for BRCA1 NM_007294.3:c.5074G>A, a MISSENSE variant, produced a function score of -1.86, 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)
|
Comment:
The BRCA1 c.5074G>A (p.Asp1692Asn) missense change affects the last nucleotide of exon 16 and is predicted to abolish the native splice donor site. An in vitro study demonstrated that this variant leads to multiple aberrant transcripts, including one causing exon 17 skipping and another causing activation of a cryptic splice donor site that leads to an in-frame retention of 153 bp of intron 17 (PMID: 25724305). These published findings are also supported by internal data. This variant has been reported in individuals with a personal and/or family history of breast and/or ovarian cancer (PMID: 8460636, 9452084, 10196379, 15571962). It is commonly reported in individuals of Icelandic ancestry and genetic linkage analysis suggests that this is an Icelandic founder mutation (PMID: 8460636, 9452084, 15571962). It is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). In summary, this variant meets criteria to be classified as likely pathogenic.
Comment:
This missense variant replaces aspartic acid with asparagine at codon 1692 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. Functional RNA studies have shown that this variant causes a splicing defect leading to skipping of exon 16 or in-frame retention of part of intron 15 (PMID: 25724305). This variant has been reported in individuals affected with familial breast/ovarian cancer (PMID: 9452084, 10196379, 11157798, 15571962). This variant has not been identified 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:
Variant summary: BRCA1 c.5074G>A (p.Asp1692Asn) results in a conservative amino acid change located in the BRCT domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251348 control chromosomes. c.5074G>A has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome. In families with this variant, 11 transmissions of the variant allele and 1 transmissions of the reference allele to affected individuals was reported. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function and showed that this variant results in loss of function (Findlay_2018). Eight clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (pathogenic/likely pathogenic n=7, VUS n=1). Based on the evidence outlined above, the variant was classified as pathogenic.
Comment:
Alters the last nucleotide of the exon and demonstrated to cause aberrant splicing, resulting predominantly in out-of-frame skipping of exon 17, as well as use of a cryptic splice donor site (Ahlborn et al., 2015); Described as an Icelandic founder variant which has been observed in individuals with breast or ovarian cancer (Arason et al., 1998; Bergthorsson et al., 1998; Janezic et al., 1999; Rafnar et al., 2004; Carter et al., 2018; Li et al., 2018; Zheng et al., 2018; Su et al., 2021); Published functional studies demonstrate a damaging effect: classified as non-functional based on a saturation genome editing (SGE) assay measuring cell growth (Findlay et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); Also known as 5193G>A; This variant is associated with the following publications: (PMID: 25722380, 30251169, 15235020, 25724305, 9452084, 20378548, 11157798, 20516115, 15571962, 15172985, 17305420, 23239986, 25748678, 24772314, 10196379, 27495310, 21447777, 16267036, 28726806, 29446198, 23199084, 21769658, 21147198, 12531920, 30078507, 30322717, 9500438, 29996917, 29884841, 32546644, 35665744, 32211327, 30130155, 9643283, 34917121, 36068545, 35171259, 25348405, 30209399)
Comment:
The c.5074G>A variant (also known as p.D1692N), located in coding exon 15 of the BRCA1 gene, results from a G to A substitution at nucleotide position 5074. The amino acid change results in aspartic acid to asparagine at codon 1692, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 15, which makes it likely to have some effect on normal mRNA splicing. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Minigene RNA analysis shows that this variant results in the skipping of exon 17 and to use a cryptic splice donor site 153 base pairs of the 5' end of intron 17, the aberrant effect of which is also observed in a haploid cell survival assay (Ahlborn LB, et al. Breast Cancer Res.Treat. 2015;150(2):289-98; Findlay GM. Nature. 2018 10;562(7726):217-222). This alteration segregated with disease in a large family and is considered an Icelandic founder mutation (Bergthorsson JT, et al. Hum. Mutat. 1998 ; Suppl 1():S195-7). Functional and computational analyses of this variant at the protein level largely reflect the missense change to be tolerated (Abkevich V, et al. J. Med. Genet. 2004;41(7):492-507; Rowling PJ, et al. J. Biol. Chem. 2010;285(26):20080-7; Lee MS, et al. Cancer Res. 2010;70(12):4880-90; Vallon-Christersson J, et al. Hum. Mol. Genet. 2001;10(4):353-60; Bouwman P et al. Clin Cancer Res, 2020 Sep;26:4559-4568; Gaboriau DC et al. Biochem J, 2015 Mar;466:613-24). Of note, this alteration is also designated as 5193G>A in published literature. The nucleotide and amino acid positions are highly conserved in available vertebrate species. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Comment:
This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1692 of the BRCA1 protein (p.Asp1692Asn). This variant also falls at the last nucleotide of exon 16, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast and/or ovarian cancer (PMID: 8460636, 9452084, 10196379, 15571962). It is commonly reported in individuals of Icelandic ancestry (PMID: 8460636, 9452084, 15571962). This variant is also known as 5193G>A. ClinVar contains an entry for this variant (Variation ID: 37632). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects BRCA1 function (PMID: 25748678, 30209399). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Comment:
The variant NM_007294.4:c.5074G>A (chr17:43067608) in BRCA1 was detected in 26 heterozygotes out of 58K WGS Icelanders (MAF= 0,022%). Following imputation in a set of 166K Icelanders (70 imputed heterozygotes) we observed an association with breast cancer using 6908 cases and 292623 controls (OR= 20.57, P= 8.44e-16) and ovarian cancer using 907 cases and 299709 controls (OR= 29.05, P= 2.67e-10). This variant has been reported in ClinVar previously as pathogenic/likely pathogenic. Based on ACMG criteria (PS4, PP1, PP3, PP5_Strong) this variant classifies as pathogenic.
Comment:
PS3(Strong)+PM2(Supporting)+PP3(Supporting)+PP4(Supporting) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042)
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| 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 |
| Germline pathogenic variants identified in women with ovarian tumors. | Carter NJ | Gynecologic oncology | 2018 | PMID: 30322717 |
| Accurate classification of BRCA1 variants with saturation genome editing. | Findlay GM | Nature | 2018 | PMID: 30209399 |
| BRCA germline mutations in an unselected nationwide cohort of Chinese patients with ovarian cancer and healthy controls. | Li A | Gynecologic oncology | 2018 | PMID: 30078507 |
| Protein stability versus function: effects of destabilizing missense mutations on BRCA1 DNA repair activity. | Gaboriau DC | The Biochemical journal | 2015 | PMID: 25748678 |
| Splicing analysis of 14 BRCA1 missense variants classifies nine variants as pathogenic. | Ahlborn LB | Breast cancer research and treatment | 2015 | PMID: 25724305 |
| Characterization of BRCA1 and BRCA2 splicing variants: a collaborative report by ENIGMA consortium members. | Thomassen M | Breast cancer research and treatment | 2012 | PMID: 21769658 |
| Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. | Lee MS | Cancer research | 2010 | PMID: 20516115 |
| Toward classification of BRCA1 missense variants using a biophysical approach. | Rowling PJ | The Journal of biological chemistry | 2010 | PMID: 20378548 |
| Aberrant 5' splice sites in human disease genes: mutation pattern, nucleotide structure and comparison of computational tools that predict their utilization. | Buratti E | Nucleic acids research | 2007 | PMID: 17576681 |
| Functional impact of missense variants in BRCA1 predicted by supervised learning. | Karchin R | PLoS computational biology | 2007 | PMID: 17305420 |
| 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 |
| BRCA2, but not BRCA1, mutations account for familial ovarian cancer in Iceland: a population-based study. | Rafnar T | European journal of cancer (Oxford, England : 1990) | 2004 | PMID: 15571962 |
| Analysis of missense variation in human BRCA1 in the context of interspecific sequence variation. | Abkevich V | Journal of medical genetics | 2004 | PMID: 15235020 |
| Structure-based assessment of missense mutations in human BRCA1: implications for breast and ovarian cancer predisposition. | Mirkovic N | Cancer research | 2004 | PMID: 15172985 |
| Functional analysis of BRCA1 C-terminal missense mutations identified in breast and ovarian cancer families. | Vallon-Christersson J | Human molecular genetics | 2001 | PMID: 11157798 |
| Germline BRCA1 alterations in a population-based series of ovarian cancer cases. | Janezic SA | Human molecular genetics | 1999 | PMID: 10196379 |
| A population study of mutations and LOH at breast cancer gene loci in tumours from sister pairs: two recurrent mutations seem to account for all BRCA1/BRCA2 linked breast cancer in Iceland. | Arason A | Journal of medical genetics | 1998 | PMID: 9643283 |
| Statistical features of human exons and their flanking regions. | Zhang MQ | Human molecular genetics | 1998 | PMID: 9536098 |
| Identification of a novel splice-site mutation of the BRCA1 gene in two breast cancer families: screening reveals low frequency in Icelandic breast cancer patients. | Bergthorsson JT | Human mutation | 1998 | PMID: 9452084 |
| Linkage analysis of chromosome 17q markers and breast-ovarian cancer in Icelandic families, and possible relationship to prostatic cancer. | Arason A | American journal of human genetics | 1993 | PMID: 8460636 |
| https://sge.gs.washington.edu/BRCA1/ | - | - | - | - |
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Record last updated Apr 28, 2025
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