Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000461534 | SCV000549699 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2018-03-23 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with asparagine at codon 3375 of the BRCA2 protein (p.Ser3375Asn). The serine residue is moderately conserved and there is a small physicochemical difference between serine and asparagine. This variant has not been reported in the literature in individuals with BRCA2-related disease. ClinVar contains an entry for this variant (Variation ID: 409527). 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. |
| Gene |
RCV000609346 | SCV000726492 | likely benign | not specified | 2018-01-08 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
| Ambry Genetics | RCV002451113 | SCV002615332 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-14 | criteria provided, single submitter | clinical testing | The p.S3375N variant (also known as c.10124G>A), located in coding exon 26 of the BRCA2 gene, results from a G to A substitution at nucleotide position 10124. The serine at codon 3375 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |