ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2798C>A (p.Thr933Lys)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002441480 SCV002747372 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-21 criteria provided, single submitter clinical testing The p.T933K variant (also known as c.2798C>A), located in coding exon 10 of the BRCA2 gene, results from a C to A substitution at nucleotide position 2798. The threonine at codon 933 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 RCV002441480 SCV003850145 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).
Invitae RCV003645328 SCV004437795 uncertain significance Hereditary breast ovarian cancer syndrome 2024-01-01 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 933 of the BRCA2 protein (p.Thr933Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 34326862). ClinVar contains an entry for this variant (Variation ID: 1796106). 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.

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