Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001238658 | SCV001411483 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2019-11-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 33 of the BRCA2 protein (p.Glu33Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. 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 conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 | RCV003294128 | SCV004005395 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-08 | criteria provided, single submitter | clinical testing | The p.E33K variant (also known as c.97G>A), located in coding exon 2 of the BRCA2 gene, results from a G to A substitution at nucleotide position 97. The glutamic acid at codon 33 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive. RNA studies have demonstrated that this alteration results in an incomplete splice defect; the clinical impact of this abnormal splicing is unknown at this time (Fraile-Bethencourt E et al. J Pathol, 2019 Aug;248:409-420; Ambry internal data). In addition, as a missense alteration, this variant is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Breast Care Center, |
RCV001238658 | SCV003932344 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-06-15 | no assertion criteria provided | clinical testing | It was found in two Korean female breast cancer patients who are sisters to each other in the single institution. They were both diagnosed with hormone-positive invasive ductal breast cancer at the age of 51. There is a family history of gastric cancer, with their mother being diagnosed at the age of 68 and their younger brother at the age of 47. |