ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2283A>C (p.Glu761Asp)

dbSNP: rs1567796302
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
University of Washington Department of Laboratory Medicine, University of Washington RCV000757933 SCV000886460 benign Hereditary breast ovarian cancer syndrome 2018-03-28 criteria provided, single submitter research The BRCA1 variant designated as NM_007294.2:c.2283A>C (p.E761D), historically known as 2402A>C (p.E761D) is classified as likely benign. Cosegregation analysis in one observed family was performed using analyze.myvariant.org (Rañola et al, 2018, PMID:28965303) with a likelihood ratio of 0.0001 to 1 that this allele explains the breast cancer in this family (Thompson, et al., 2003, PMID:2900794). This genomic position is not highly conserved. The variant is in a non-functional BRCA1 domain. This variant is not predicted to alter BRCA1 gene function or modify cancer risk. A pathogenic BRCA2 mutation (c.9924C>G, p.Y3308X, historically known as c.10152C>G) co-occurs with this BRCA1 variant in several relatives in the observed family with diagnoses of breast, ovarian, prostate cancer. Bayesian analysis integrating all of this data (Tavtigian et al, 2018, PMID:29300386) gives less than 0.1% probability of pathogenicity, which is consistent with a classification of benign. This analysis was performed in conjunction with the family studies project as part of the University of Washington Find My Variant Study.
Color Diagnostics, LLC DBA Color Health RCV001187961 SCV001354903 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000757933 SCV002169000 uncertain significance Hereditary breast ovarian cancer syndrome 2023-04-12 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 619018). This missense change has been observed in individual(s) with personal and/or family history of breast and ovarian cancer (PMID: 30374176). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 761 of the BRCA1 protein (p.Glu761Asp).
University of Washington Department of Laboratory Medicine, University of Washington RCV001187961 SCV003847787 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).

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