Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000129520 | SCV000184296 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-07-07 | criteria provided, single submitter | clinical testing | The c.649_655delGGAGGTCinsTGAGGTT pathogenic mutation, located in coding exon 7 of the RAD51D gene, results from a deletion of GGAGGTC and insertion of TGAGGTT between nucleotide positions 649 and 655. This results in a predicted alternate stop signal at codon 217 (p.G217*). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Labcorp Genetics |
RCV000559627 | SCV000651767 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-11-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly217*) in the RAD51D gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD51D are known to be pathogenic (PMID: 21822267). This variant is present in population databases (rs775365939, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with breast cancer and/or ovarian cancer (PMID: 26261251, 32107557). ClinVar contains an entry for this variant (Variation ID: 484764). For these reasons, this variant has been classified as Pathogenic. |
| Color Diagnostics, |
RCV000129520 | SCV001342500 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-15 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 7 of the RAD51D gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of RAD51D function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298477 | SCV002598741 | pathogenic | Hereditary breast ovarian cancer syndrome | 2022-09-01 | criteria provided, single submitter | clinical testing | Variant summary: RAD51D c.649_655delinsTGAGGTT (p.Gly217X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251422 control chromosomes. c.649_655delinsTGAGGTT has been reported in the literature in individuals affected with ovarian cancer (examples: Song_2015, Feliubadalo_2019). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV000559627 | SCV004200451 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2020-12-11 | criteria provided, single submitter | clinical testing |