Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000809306 | SCV000949453 | pathogenic | Fanconi anemia complementation group O | 2019-07-02 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 8-9 of the RAD51C gene. The 5' boundary is likely confined to intron 7. 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. A similar deletion of exons 8-9 has been observed in an individual with a personal and family history of ovarian cancer (PMID: 27616075). This variant is expected to cause the loss or disruption of 55 C-terminal amino acid residues from the RAD51C protein. While the effect of this particular sequence change on RAD51C function has not been tested, the C-terminal region of RAD51C is known to contain a nuclear localization signal, and the deletion of 11 C-terminal residues leads to cellular mislocalization of the protein and reduced MMC resistance compared to the wild-type protein (PMID: 12966089). For these reasons, this variant has been classified as Pathogenic. |