ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2282A>G (p.Tyr761Cys)

dbSNP: rs879255443
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000566368 SCV000666017 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-01 criteria provided, single submitter clinical testing The p.Y761C variant (also known as c.2282A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 2282. The tyrosine at codon 761 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000566368 SCV000912638 uncertain significance Hereditary cancer-predisposing syndrome 2019-06-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000815303 SCV000955752 uncertain significance Hereditary breast ovarian cancer syndrome 2024-12-03 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 761 of the BRCA2 protein (p.Tyr761Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 481526). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001800775 SCV002046254 uncertain significance not provided 2020-09-30 criteria provided, single submitter clinical testing
GeneDx RCV001800775 SCV003195072 uncertain significance not provided 2022-07-22 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; Also known as 2510A>G
University of Washington Department of Laboratory Medicine, University of Washington RCV000566368 SCV003848196 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).
BRCAlab, Lund University RCV003493654 SCV004244244 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2020-03-02 no assertion criteria provided clinical testing

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