Total submissions: 10
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001568554 | SCV007113344 | uncertain significance | not provided | 2025-02-21 | criteria provided, single submitter | clinical testing | The RAD51D c.871C>T (p.Arg291Cys) variant has been reported in the published literature in in a large scale breast cancer association study in breast cancer cases as well as in reportedly healthy individuals (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/)). The frequency of this variant in the general population (Genome Aggregation Database, http://gnomad.broadinstitute.org) is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Department of Pathology and Laboratory Medicine, |
RCV005361288 | SCV005912323 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-02-18 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000475686 | SCV004208069 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-01-23 | criteria provided, single submitter | clinical testing | |
| MGZ Medical Genetics Center | RCV000475686 | SCV002580585 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2021-12-30 | criteria provided, single submitter | clinical testing | |
| Institute for Clinical Genetics, |
RCV001568554 | SCV002010690 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001568554 | SCV001792447 | uncertain significance | not provided | 2021-06-23 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21111057, 14704354, 19327148, 27535533) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174934 | SCV001338383 | uncertain significance | not specified | 2020-02-24 | criteria provided, single submitter | clinical testing | Variant summary: RAD51D c.871C>T (p.Arg291Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251390 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.871C>T in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Color Diagnostics, |
RCV000216279 | SCV000908944 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-10 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 291 of the RAD51D 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 detected in a breast cancer case-control meta-analysis in 3/60463 cases and 2/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID RAD51D_000074). This variant has been identified in 3/251390 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. |
| Labcorp Genetics |
RCV000475686 | SCV000551342 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2025-12-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 291 of the RAD51D protein (p.Arg291Cys). This variant is present in population databases (rs372038369, gnomAD 0.007%). 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: 231161). 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%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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 | RCV000216279 | SCV000274921 | uncertain significance | Hereditary cancer-predisposing syndrome | 2025-04-07 | criteria provided, single submitter | clinical testing | The p.R291C variant (also known as c.871C>T), located in coding exon 9 of the RAD51D gene, results from a C to T substitution at nucleotide position 871. The arginine at codon 291 is replaced by cysteine, an amino acid with highly dissimilar 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. |