ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4130A>G (p.Asn1377Ser)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002296728 SCV002595438 uncertain significance Hereditary breast ovarian cancer syndrome 2023-06-19 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. 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. ClinVar contains an entry for this variant (Variation ID: 1718958). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is present in population databases (rs749624669, gnomAD 0.003%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1377 of the BRCA2 protein (p.Asn1377Ser).
University of Washington Department of Laboratory Medicine, University of Washington RCV003157157 SCV003848706 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).
Ambry Genetics RCV003157157 SCV004052515 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-21 criteria provided, single submitter clinical testing The p.N1377S variant (also known as c.4130A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 4130. The asparagine at codon 1377 is replaced by serine, an amino acid with highly similar properties. This amino acid position is not 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.
All of Us Research Program, National Institutes of Health RCV004005604 SCV004827126 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-06-28 criteria provided, single submitter clinical testing

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