ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.9997C>G (p.Leu3333Val)

gnomAD frequency: 0.00001  dbSNP: rs567476314
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132264 SCV000187347 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-22 criteria provided, single submitter clinical testing The p.L3333V variant (also known as c.9997C>G), located in coding exon 26 of the BRCA2 gene, results from a C to G substitution at nucleotide position 9997. The leucine at codon 3333 is replaced by valine, 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000232518 SCV000283377 uncertain significance Hereditary breast ovarian cancer syndrome 2024-12-18 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3333 of the BRCA2 protein (p.Leu3333Val). This variant is present in population databases (rs567476314, gnomAD 0.003%). 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: 142831). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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.
Counsyl RCV000662506 SCV000785035 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2017-03-24 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000679200 SCV000805804 uncertain significance not provided 2018-01-08 criteria provided, single submitter clinical testing
GeneDx RCV000679200 SCV000972568 likely benign not provided 2018-06-04 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679200 SCV001133997 uncertain significance not provided 2019-02-14 criteria provided, single submitter clinical testing

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