Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000045380 | SCV000073393 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-04-23 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 2666 of the BRCA2 protein (p.Arg2666Thr). This variant is not present in population databases (gnomAD no frequency). 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: 52466). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA2 protein function with a negative predictive value of 95%. 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 | RCV000561371 | SCV000665976 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-11 | criteria provided, single submitter | clinical testing | The p.R2666T variant (also known as c.7997G>C), located in coding exon 17 of the BRCA2 gene, results from a G to C substitution at nucleotide position 7997. The arginine at codon 2666 is replaced by threonine, an amino acid with similar properties. This alteration is predicted to be neutral based on a computational method that produces a probabilistic likelihood ratio predictive of whether a missense variant impairs protein function (Karchin R et al. Cancer Inform. 2008;6:203-16). This amino acid position is poorly 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. |
| Color Diagnostics, |
RCV000561371 | SCV000689089 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-26 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV004566843 | SCV005058992 | uncertain significance | Familial cancer of breast | 2024-03-15 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV005229864 | SCV005877203 | uncertain significance | not provided | 2024-10-07 | criteria provided, single submitter | clinical testing | The BRCA2 c.7997G>C; p.Arg2666Thr variant (rs80359033), to our knowledge, is not reported in the medical literature associated with disease but is reported in ClinVar (Variation ID: 52466). This variant is absent from the Genome Aggregation Database (v2.1.1), indicating it is not a common polymorphism. Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.587), but is predicted to be neutral in a protein likelihood ratio analysis (Karchin 2008). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Karchin R et al. Classifying Variants of Undetermined Significance in BRCA2 with protein likelihood ratios. Cancer Inform. 2008;6:203-16. PMID: 19043619. |
| Breast Cancer Information Core |
RCV000113854 | SCV000147246 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-05-29 | no assertion criteria provided | clinical testing |