Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000816764 | SCV000957288 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-08-30 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 17 of the RAD51D protein (p.Ile17Val). This variant is not present in population databases (gnomAD no frequency). 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: 659719). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000986016 | SCV001134803 | uncertain significance | not provided | 2024-10-09 | criteria provided, single submitter | clinical testing | The RAD51D c.49A>G (p.Ile17Val) variant has not been reported in individuals with RAD51D-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). 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. |
| Color Diagnostics, |
RCV001183136 | SCV001348793 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 17 of the RAD51D protein. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). 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. |
| Genetic Services Laboratory, |
RCV001816897 | SCV002066151 | uncertain significance | not specified | 2021-09-21 | criteria provided, single submitter | clinical testing | DNA sequence analysis of the RAD51D gene demonstrated a sequence change, c.49A>G, in exon 1 that results in an amino acid change, p.Ile17Val. This sequence change has not been described in population databases including gnomAD and ExAC (dbSNP rs1002032036). The p.Ile17Val change affects a poorly conserved amino acid residue located in a domain of the RAD51D protein that is known to be functional. The p.Ile17Val substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in individuals with RAD51D-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Ile17Val change remains unknown at this time. |
| Ambry Genetics | RCV001183136 | SCV002642374 | likely benign | Hereditary cancer-predisposing syndrome | 2020-02-24 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Baylor Genetics | RCV000816764 | SCV005054047 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 4 | 2023-11-09 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001816897 | SCV005202652 | uncertain significance | not specified | 2024-07-11 | criteria provided, single submitter | clinical testing |