ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.10043A>G (p.Asn3348Ser)

gnomAD frequency: 0.00001  dbSNP: rs761094613
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000196085 SCV000254165 uncertain significance Hereditary breast ovarian cancer syndrome 2022-09-22 criteria provided, single submitter clinical testing 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. This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 3348 of the BRCA2 protein (p.Asn3348Ser). This variant is present in population databases (rs761094613, gnomAD 0.01%). This missense change has been observed in individual(s) with BRCA2-related conditions (PMID: 30093976). ClinVar contains an entry for this variant (Variation ID: 216238). 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.
Ambry Genetics RCV003278696 SCV004005468 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-10 criteria provided, single submitter clinical testing The p.N3348S variant (also known as c.10043A>G), located in coding exon 26 of the BRCA2 gene, results from an A to G substitution at nucleotide position 10043. The asparagine at codon 3348 is replaced by serine, an amino acid with highly similar properties. This alteration has been reported as a mutation in an individual from a cohort of 1191 cancer index patients who underwent clinical evaluation and testing with multigene panels (Chan GHJ et al. Oncotarget, 2018 Jul;9:30649-30660). This amino acid position is well 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.

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