ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.950C>A (p.Thr317Lys)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002374171 SCV002688413 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-11 criteria provided, single submitter clinical testing The p.T317K variant (also known as c.950C>A), located in coding exon 9 of the BRCA2 gene, results from a C to A substitution at nucleotide position 950. The threonine at codon 317 is replaced by lysine, 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 RCV002374171 SCV003848154 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).
Labcorp Genetics (formerly Invitae), Labcorp RCV005097348 SCV005734575 uncertain significance Hereditary breast ovarian cancer syndrome 2024-04-07 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 317 of the BRCA2 protein (p.Thr317Lys). 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: 1767210). 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.
PreventionGenetics, part of Exact Sciences RCV004545311 SCV004796797 uncertain significance BRCA2-related disorder 2024-02-02 no assertion criteria provided clinical testing The BRCA2 c.950C>A variant is predicted to result in the amino acid substitution p.Thr317Lys. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. This variant occurs within a region of the BRCA2 gene that is predicted to be tolerant to missense variation (Table 2, Dines et al. 2020. PubMed ID: 31911673). This variant has interpretations of uncertain and likely benign in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/1767210/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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