ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9742A>G (p.Met3248Val)

dbSNP: rs876659778
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001212485 SCV001384069 uncertain significance Hereditary breast ovarian cancer syndrome 2023-12-17 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3248 of the BRCA2 protein (p.Met3248Val). 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: 942488). 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.
Ambry Genetics RCV002379803 SCV002693416 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-01 criteria provided, single submitter clinical testing The p.M3248V variant (also known as c.9742A>G), located in coding exon 26 of the BRCA2 gene, results from an A to G substitution at nucleotide position 9742. The methionine at codon 3248 is replaced by valine, an amino acid with highly similar 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.
Baylor Genetics RCV003462712 SCV004216154 uncertain significance Familial cancer of breast 2023-05-10 criteria provided, single submitter clinical testing

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