ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3098A>T (p.Asp1033Val)

gnomAD frequency: 0.00001  dbSNP: rs141702094
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236981 SCV000293564 uncertain significance not provided 2023-10-20 criteria provided, single submitter clinical testing Observed in an individual undergoing multi-gene panel testing based on personal and family history of cancer (PMID: 31853058); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as 3326A>T; This variant is associated with the following publications: (PMID: 29884841, 32377563, 9002670, 22193408, 31853058)
Labcorp Genetics (formerly Invitae), Labcorp RCV000474695 SCV000549653 uncertain significance Hereditary breast ovarian cancer syndrome 2024-06-10 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with valine, which is neutral and non-polar, at codon 1033 of the BRCA2 protein (p.Asp1033Val). This variant is present in population databases (rs141702094, gnomAD 0.008%). 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: 246140). 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.
Ambry Genetics RCV000570313 SCV000665385 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-26 criteria provided, single submitter clinical testing The p.D1033V variant (also known as c.3098A>T), located in coding exon 10 of the BRCA2 gene, results from an A to T substitution at nucleotide position 3098. The aspartic acid at codon 1033 is replaced by valine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236981 SCV001133735 uncertain significance not provided 2019-03-22 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine, University of Washington RCV000570313 SCV003851682 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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