ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7817A>G (p.Asp2606Gly)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002409971 SCV002669611 uncertain significance Hereditary cancer-predisposing syndrome 2022-05-24 criteria provided, single submitter clinical testing The p.D2606G variant (also known as c.7817A>G), located in coding exon 16 of the BRCA2 gene, results from an A to G substitution at nucleotide position 7817. The aspartic acid at codon 2606 is replaced by glycine, an amino acid with similar properties. This variant had intermediate function in a homology-directed DNA repair (HDR) assay (Hart SN et al. Genet Med, 2019 01;21:71-80). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003645301 SCV004538902 uncertain significance Hereditary breast ovarian cancer syndrome 2024-10-13 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 2606 of the BRCA2 protein (p.Asp2606Gly). 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: 1760752). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BRCA2 protein function. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BRCA2 function (PMID: 29394989). 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.

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