Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000566222 | SCV000667159 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-01 | criteria provided, single submitter | clinical testing | The p.R255K variant (also known as c.764G>A), located in coding exon 9 of the RAD51D gene, results from a G to A substitution at nucleotide position 764. The arginine at codon 255 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is well 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000590504 | SCV000698113 | uncertain significance | not provided | 2016-07-15 | criteria provided, single submitter | clinical testing | Variant summary: The RAD51D c.764G>A (p.Arg255Lys) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant is absent in 121128 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available. |
| Labcorp Genetics |
RCV000686177 | SCV000813681 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-09-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 255 of the RAD51D protein (p.Arg255Lys). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. ClinVar contains an entry for this variant (Variation ID: 482193). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt RAD51D 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 |
RCV000590504 | SCV003927529 | uncertain significance | not provided | 2023-05-25 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 19327148) |
| Baylor Genetics | RCV000686177 | SCV005053989 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-03-28 | criteria provided, single submitter | clinical testing |