ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.6374C>A (p.Thr2125Asn)

dbSNP: rs776937022
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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 RCV001218388 SCV001390269 uncertain significance Hereditary breast ovarian cancer syndrome 2022-03-08 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 2125 of the BRCA2 protein (p.Thr2125Asn). This variant is present in population databases (rs776937022, gnomAD 0.005%). 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: 947329). 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. 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.
GeneDx RCV001751413 SCV002005473 uncertain significance not provided 2019-04-11 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002365988 SCV002659068 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-08 criteria provided, single submitter clinical testing The p.T2125N variant (also known as c.6374C>A), located in coding exon 10 of the BRCA2 gene, results from a C to A substitution at nucleotide position 6374. The threonine at codon 2125 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV002365988 SCV003852471 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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