ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1777G>T (p.Ala593Ser)

dbSNP: rs431825286
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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 RCV000562320 SCV000661337 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-18 criteria provided, single submitter clinical testing The p.A593S variant (also known as c.1777G>T), located in coding exon 9 of the BRCA2 gene, results from a G to T substitution at nucleotide position 1777. The alanine at codon 593 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and serine is the reference amino acid in multiple other 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 RCV000637708 SCV000759180 uncertain significance Hereditary breast ovarian cancer syndrome 2022-11-14 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. 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. 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: 96770). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 593 of the BRCA2 protein (p.Ala593Ser).
University of Washington Department of Laboratory Medicine, University of Washington RCV000562320 SCV003851634 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 RCV000082891 SCV004839427 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2023-12-01 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV004595916 SCV005090019 likely benign not specified 2024-07-31 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000082891 SCV000114965 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 2 2009-07-17 no assertion criteria provided clinical testing

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