Total submissions: 5
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 | 2023-11-27 | criteria provided, single submitter | clinical testing | The c.905-3_906delCAGGG variant results from a deletion of 5 nucleotides between positions c.905-3 and c.906 and involves the canonical splice acceptor site before coding exon 7 of the RAD51C gene. This variant has been observed in an individual with breast cancer (Susswein LR et al. Genet Med. 2016:18(8):823-32). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). The canonical splice acceptor site is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. In a functional RNA study, this variant was associated with exon 7 skipping (Sanoguera-Miralles L et al. Cancers (Basel), 2022 Jun;14: Ambry internal data). 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. |
Labcorp Genetics |
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 | |
Myriad Genetics, |
RCV003462105 | SCV004931482 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 3 | 2024-01-03 | criteria provided, single submitter | clinical testing | This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function. |