Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000527833 | SCV000651733 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-12-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln115*) 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 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: 472599). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Color Diagnostics, |
RCV000777271 | SCV000912973 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-01-09 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamine with a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. In addition, this variant has been shown to affect splicing in a mini-gene assay and in a breast cancer cell line, resulting in multiple abnormal transcripts including out-of-frame deletion of exon 4 or exons 4-5, as well as in-frame deletion of exons 3-5 that encode a functionally important ATPase domain (PMID: 34200360). 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. |
Sema4, |
RCV000777271 | SCV002534798 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-01-25 | criteria provided, single submitter | curation | |
Ambry Genetics | RCV000777271 | SCV002615197 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-08-28 | criteria provided, single submitter | clinical testing | The p.Q115* pathogenic mutation (also known as c.343C>T), located in coding exon 4 of the RAD51D gene, results from a C to T substitution at nucleotide position 343. This changes the amino acid from a glutamine to a stop codon within coding exon 4. 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. |
Myriad Genetics, |
RCV000527833 | SCV004933231 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 4 | 2024-01-04 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |