Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001019589 | SCV001180968 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-12 | criteria provided, single submitter | clinical testing | The p.M3217K variant (also known as c.9650T>A), located in coding exon 26 of the BRCA2 gene, results from a T to A substitution at nucleotide position 9650. The methionine at codon 3217 is replaced by lysine, an amino acid with similar properties. This alteration was detected on a 25-gene panel test in a woman of Western/Northern European ancestry who was diagnosed with breast cancer before age 50 (Tung N et al. Cancer, 2015 Jan;121:25-33). In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice acceptor site. RNA studies have demonstrated that this alteration does not result in abnormal splicing in the set of samples tested (Ambry internal data). 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. |
| Gene |
RCV001571271 | SCV001795709 | uncertain significance | not provided | 2019-06-12 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 25451944) |
| Labcorp Genetics |
RCV001860951 | SCV002286771 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-05-04 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 3217 of the BRCA2 protein (p.Met3217Lys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 823383). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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. |
| Baylor Genetics | RCV004569981 | SCV005059175 | uncertain significance | Familial cancer of breast | 2023-11-23 | criteria provided, single submitter | clinical testing |