Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001032990 | SCV001196297 | likely pathogenic | Fanconi anemia complementation group O | 2019-05-19 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exon 9 of the RAD51C gene. The 5' boundary is likely confined to intron 8. The 3' end of this event is unknown as it extends through the termination codon beyond the assayed region for this gene and may encompass additional genes. While this deletion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated protein product or disrupt mRNA translation. This variant has not been reported in the literature in individuals with RAD51C-related disease. This variant is expected to delete a portion of the C-terminal region of the RAD51C protein containing the nuclear localization signal (NLS) (residues Arg366-Leu376) (PMID: 12966089). Although functional studies have not been performed for this particular variant, disruption of the NLS likely impairs RAD51C function and suggests that deletion of this region of the CHEK2 protein is causative of disease. 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. |