Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000460712 | SCV000550209 | uncertain significance | Fanconi anemia complementation group O | 2024-01-28 | 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 253 of the RAD51C protein (p.Asp253Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer and/or ovarian cancer (PMID: 28202063, 34923718). ClinVar contains an entry for this variant (Variation ID: 409850). 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 with a negative predictive value of 80%. 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. |
| Gene |
RCV000481758 | SCV000569624 | uncertain significance | not provided | 2020-10-28 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28202063) |
| Ambry Genetics | RCV000566748 | SCV000667102 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-18 | criteria provided, single submitter | clinical testing | The p.D253G variant (also known as c.758A>G), located in coding exon 5 of the RAD51C gene, results from an A to G substitution at nucleotide position 758. The aspartic acid at codon 253 is replaced by glycine, an amino acid with similar properties. This amino acid position is 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. |
| Color Diagnostics, |
RCV000566748 | SCV000686385 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-15 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with glycine at codon 253 of the RAD51C protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer (PMID: 28202063). This variant has been identified in 1/251444 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Baylor Genetics | RCV003470462 | SCV004207923 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 3 | 2023-10-03 | criteria provided, single submitter | clinical testing |