ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.4726C>G (p.Leu1576Val)

gnomAD frequency: 0.00002  dbSNP: rs758051329
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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 RCV001022957 SCV001184758 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-01 criteria provided, single submitter clinical testing The p.L1576V variant (also known as c.4726C>G), located in coding exon 10 of the BRCA2 gene, results from a C to G substitution at nucleotide position 4726. The leucine at codon 1576 is replaced by valine, an amino acid with highly similar properties. This amino acid position is poorly 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.
Invitae RCV002298841 SCV002589958 uncertain significance Hereditary breast ovarian cancer syndrome 2022-09-23 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 825127). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. This variant is present in population databases (rs758051329, gnomAD 0.004%). This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1576 of the BRCA2 protein (p.Leu1576Val). 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.
University of Washington Department of Laboratory Medicine, University of Washington RCV001022957 SCV003852049 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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