ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4034A>G (p.Asp1345Gly)

dbSNP: rs2137502285
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001581786 SCV001811752 uncertain significance not provided 2019-10-11 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 a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001866138 SCV002208802 uncertain significance Hereditary breast ovarian cancer syndrome 2024-04-30 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1345 of the BRCA2 protein (p.Asp1345Gly). 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: 1213637). 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 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV003158907 SCV003848625 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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