ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1733G>A (p.Gly578Asp)

dbSNP: rs398122730
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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 RCV000166334 SCV000217120 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-29 criteria provided, single submitter clinical testing The p.G578D variant (also known as c.1733G>A), located in coding exon 9 of the BRCA2 gene, results from a G to A substitution at nucleotide position 1733. The glycine at codon 578 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000166334 SCV000688720 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-05 criteria provided, single submitter clinical testing This missense variant replaces glycine with aspartic acid at codon 578 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in 1 individual affected with breast cancer (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_007879). This variant has been identified in 1/250840 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001854359 SCV002113050 uncertain significance Hereditary breast ovarian cancer syndrome 2023-10-09 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 578 of the BRCA2 protein (p.Gly578Asp). This variant is present in population databases (rs398122730, 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: 91756). 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. 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 RCV000166334 SCV003851601 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).
All of Us Research Program, National Institutes of Health RCV004804071 SCV004846952 uncertain significance BRCA2-related cancer predisposition 2024-02-22 criteria provided, single submitter clinical testing This missense variant replaces glycine with aspartic acid at codon 578 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in 1 individual affected with breast cancer (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_007879). This variant has been identified in 1/250840 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Sharing Clinical Reports Project (SCRP) RCV000077664 SCV000109467 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2007-07-05 no assertion criteria provided clinical testing

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