Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000529943 | SCV000635215 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2021-08-13 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glycine at codon 762 of the BRCA2 protein (p.Asp762Gly). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This missense change has been observed in individual(s) with clinical features of BRCA2-related conditions (PMID: 28039656). ClinVar contains an entry for this variant (Variation ID: 462263). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glycine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. |
Ambry Genetics | RCV002448667 | SCV002735512 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-01-20 | criteria provided, single submitter | clinical testing | The p.D762G variant (also known as c.2285A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 2285. The aspartic acid at codon 762 is replaced by glycine, an amino acid with 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. |
University of Washington Department of Laboratory Medicine, |
RCV002448667 | SCV003848197 | 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). |