Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000471166 | SCV000550205 | uncertain significance | Fanconi anemia complementation group O | 2023-10-17 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 202 of the RAD51C protein (p.Asp202Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 26976419). ClinVar contains an entry for this variant (Variation ID: 409847). 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 RAD51C protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a 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. |
| Ambry Genetics | RCV001024846 | SCV001186933 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-16 | criteria provided, single submitter | clinical testing | The p.D202G variant (also known as c.605A>G), located in coding exon 4 of the RAD51C gene, results from an A to G substitution at nucleotide position 605. The aspartic acid at codon 202 is replaced by glycine, an amino acid with similar properties. This alteration has been reported in a cohort of 488 patients with stages I to III breast cancer who were tested with a 25-gene panel test (Tung N et al. J. Clin. Oncol., 2016 May;34:1460-8). This amino acid position is poorly 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. |
| Baylor Genetics | RCV003470461 | SCV004208019 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-02-09 | criteria provided, single submitter | clinical testing |