Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000467585 | SCV000550196 | pathogenic | Fanconi anemia complementation group O | 2023-11-20 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 7 of the RAD51C gene. It does not directly change the encoded amino acid sequence of the RAD51C protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs774586107, gnomAD 0.0009%). This variant has been observed in individual(s) with breast or ovarian cancer (PMID: 22725699, 33011440). ClinVar contains an entry for this variant (Variation ID: 409841). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 22725699, 33011440, 33333735). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000571578 | SCV000663788 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-06-12 | criteria provided, single submitter | clinical testing | The c.965+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 7 in the RAD51C gene. This alteration has previously been reported in an individual diagnosed with ovarian cancer at age 51, who also had a family history of breast cancer, including male breast cancer (Coulet F et al. Clin. Genet. 2013 Apr;83:332-6). 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. Functional RNA studies have demonstrated that this alteration results in out-of-frame exon skipping and premature protein truncation (Coulet F et al. Clin. Genet. 2013 Apr;83:332-6; Sanoguera-Miralles L et al. Cancers (Basel), 2020 Dec;12; Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Color Diagnostics, |
RCV000571578 | SCV000686408 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-03-21 | criteria provided, single submitter | clinical testing | This variant causes a G to A nucleotide substitution at the +5 position of intron 7 of the RAD51C gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 22725699, 33011440, 36329109). RNA studies using RT-PCR analysis of a patient sample and mini-gene assays have shown that this variant causes out-of-frame skipping of exon 7 (PMID: 22725699, 33011440, 33333735), which is expected to create a frameshift and premature translation stop signal resulting in an absent or non-functional protein product. This variant has been identified in 1/251118 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of RAD51C function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Likely Pathogenic. |
| Baylor Genetics | RCV004568045 | SCV005053957 | likely pathogenic | Breast-ovarian cancer, familial, susceptibility to, 3 | 2024-02-05 | criteria provided, single submitter | clinical testing |