Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000706668 | SCV000835733 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-05-02 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces glutamic acid with glycine at codon 1035 of the BRCA2 protein (p.Glu1035Gly). The glutamic acid residue is moderately conserved and there is a moderate physicochemical difference between glutamic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |
University of Washington Department of Laboratory Medicine, |
RCV003158082 | SCV003851687 | 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). |
Ambry Genetics | RCV003158082 | SCV005097540 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-06-06 | criteria provided, single submitter | clinical testing | The p.E1035G variant (also known as c.3104A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 3104. The glutamic acid at codon 1035 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear. |