Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000160935 | SCV000211642 | pathogenic | not provided | 2023-10-23 | criteria provided, single submitter | clinical testing | Canonical splice site variant demonstrated to result in complete skipping of exon 7 and predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease (PMID: 35740625); Observed in individuals with breast cancer (PMID: 26681312); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 35740625, 26681312) |
| Ambry Genetics | RCV000570045 | SCV000671917 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-01-21 | criteria provided, single submitter | clinical testing | The c.905-3_906delCAGGG variant, located at the 5' boundary of coding exon 7 of the RAD51C gene, results from a deletion of 5 nucleotides at positions 905-3 to 906. This deletion spans the canonical splice acceptor site sequence, and is is well conserved in available vertebrate species. Alterations affecting the same splice acceptor site have been reported in the literature. For example, the c.905-2delAG alteration was identified in a 52 year old woman with endometrioid cancer (Song H et al. J. Clin. Oncol 2015:33(26):2901-7) and the c.905-2A>G alteration was reported in a patient with ovarian cancer and shown to cause skipping of exon 7 in splicing assays (Coulet F et al. Clin. Genet. 2013:83(4):332-6). Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Invitae | RCV000701513 | SCV000830316 | pathogenic | Fanconi anemia complementation group O | 2023-11-28 | criteria provided, single submitter | clinical testing | This variant results in the deletion of exon 7 (c.905-3_906del) of the RAD51C gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917, 29278735). This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with breast cancer (PMID: 26681312). ClinVar contains an entry for this variant (Variation ID: 182846). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003462105 | SCV004208058 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 3 | 2021-06-29 | criteria provided, single submitter | clinical testing |