Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000571657 | SCV000663791 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-05-13 | criteria provided, single submitter | clinical testing | The c.904+1G>T intronic variant results from a G to T substitution one nucleotide after coding exon 6 of the RAD51C gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000986014 | SCV001134793 | likely pathogenic | not provided | 2018-11-21 | criteria provided, single submitter | clinical testing | The variant disrupts a canonical splice site, and is therefore predicted to result in the loss of a functional protein. Not found in the total gnomAD dataset, and the data is high quality (0/276968 chr). |
| Invitae | RCV001047716 | SCV001211695 | likely pathogenic | Fanconi anemia complementation group O | 2021-07-07 | criteria provided, single submitter | clinical testing | 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. Donor and acceptor splice site variants 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). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 480510). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 6 of the RAD51C gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
| Sema4, |
RCV000571657 | SCV002530030 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-02-22 | criteria provided, single submitter | curation | |
| Baylor Genetics | RCV003459305 | SCV004208036 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 3 | 2022-06-16 | criteria provided, single submitter | clinical testing |