Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000777161 | SCV000912852 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-03-29 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001063152 | SCV001227987 | pathogenic | Fanconi anemia complementation group O | 2023-02-14 | criteria provided, single submitter | clinical testing | Studies have shown that disruption of this splice site results in skipping of exon 5, but is expected to preserve the integrity of the reading-frame (PMID: 22006311, 24139550, 33333735). This sequence change affects an acceptor splice site in intron 4 of the RAD51C gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with breast cancer and ovarian cancer (PMID: 22006311, 22538716, 24549055, 25452441, 26261251, 26681312, 29255180, 31300551). ClinVar contains an entry for this variant (Variation ID: 631112). This variant disrupts a region of the RAD51C protein in which other variant(s) (p.Arg258His) have been determined to be pathogenic (PMID: 20400963, 22167183, 26354865). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV000777161 | SCV002661541 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2017-10-13 | criteria provided, single submitter | clinical testing | The c.706-2A>C intronic variant results from an A to C substitution two nucleotides upstream from coding exon 5 in the RAD51C gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
Fulgent Genetics, |
RCV002501009 | SCV002809891 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O | 2021-12-06 | criteria provided, single submitter | clinical testing | |
Leiden Open Variation Database | RCV001195023 | SCV001365270 | pathogenic | not provided | 2019-12-23 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Florentia Fostira. |