ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2633A>G (p.Asp878Gly)

dbSNP: rs765618026
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000697478 SCV000826091 uncertain significance Hereditary breast ovarian cancer syndrome 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 878 of the BRCA2 protein (p.Asp878Gly). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
GeneDx RCV001555337 SCV001776739 uncertain significance not provided 2019-07-23 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001797785 SCV002041831 uncertain significance not specified 2021-11-05 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV003158048 SCV003848464 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).
All of Us Research Program, National Institutes of Health RCV003999666 SCV004845039 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-06-08 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glycine at codon 878 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA2-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). 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.

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