Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000793447 | SCV000932799 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-11-12 | 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. 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 asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with BRCA2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with asparagine at codon 1979 of the BRCA2 protein (p.Ser1979Asn). The serine residue is moderately conserved and there is a small physicochemical difference between serine and asparagine. |
Ambry Genetics | RCV002352317 | SCV002649931 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-12 | criteria provided, single submitter | clinical testing | The p.S1979N variant (also known as c.5936G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 5936. The serine at codon 1979 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
University of Washington Department of Laboratory Medicine, |
RCV002352317 | SCV003850797 | 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). |