Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000581874 | SCV000691349 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-04-03 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001853941 | SCV002261849 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-04-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu215Thrfs*112) in the RAD51D gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 114 amino acid(s) of the RAD51D protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 492434). This variant disrupts the ATPase domain and RAD51C interaction domain of the RAD51D protein, which are necessary for the DNA repair activity (PMID: 14704354, 19327148, 21111057, 10749867). While functional studies have not been performed to directly test the effect of this variant on RAD51D protein function, this suggests that disruption of this region of the protein is causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Ambry Genetics | RCV000581874 | SCV002658913 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-06-21 | criteria provided, single submitter | clinical testing | The c.641dupC variant, located in coding exon 7 of the RAD51D gene, results from a duplication of C at nucleotide position 641, causing a translational frameshift with a predicted alternate stop codon (p.L215Tfs*112). This alteration occurs at the 3' terminus of theRAD51D gene, is not expected to trigger nonsense-mediated mRNA decay, and impacts the last 114 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Myriad Genetics, |
RCV001853941 | SCV004189567 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2023-11-30 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. |
| Baylor Genetics | RCV001853941 | SCV004200438 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2022-06-20 | criteria provided, single submitter | clinical testing |