Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000709514 | SCV000839338 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000772310 | SCV000905428 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-02-27 | criteria provided, single submitter | clinical testing | This variant causes a T to C nucleotide substitution at the +2 position of intron 5 of the RAD51C gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is expected to result in an absent or disrupted protein product. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified 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. |
| Mendelics | RCV000989963 | SCV001140723 | likely pathogenic | Fanconi anemia complementation group O | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000772310 | SCV002678731 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-06-15 | criteria provided, single submitter | clinical testing | The c.837+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 5 in the RAD51C gene. Alterations that disrupt the canonical splice site are expected to result in aberrant splicing. In a functional RNA study, this variant was associated with in-frame exon 5 skipping; however, splicing was tested using a mini gene assay and patient RNA was not analyzed (Sanoguera-Miralles L et al. Cancers (Basel), 2020 Dec;12:). In silico splice site analysis predicts that this alteration will weaken the native splice donor site. The resulting transcript is predicted to be in-frame and is not expected to trigger nonsense-mediated mRNAdecay. The exact functional effect of the altered amino acid sequence is unknown; however, the impacted region is critical for protein function (Drexler GA et al. DNA Repair (Amst.) 2004 Oct;3(10):1335-43)). This nucleotide position is highly conserved in available vertebrate species. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |