Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000464633 | SCV000548051 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-10-12 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 23 (c.3612_3618+5del) of the RAD50 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RAD50 are known to be pathogenic (PMID: 19409520). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. ClinVar contains an entry for this variant (Variation ID: 408396). Studies have shown that this variant is associated with altered splicing resulting in multiple RNA products (Invitae). 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. |
| Ambry Genetics | RCV000464633 | SCV000663602 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2022-11-09 | criteria provided, single submitter | clinical testing | The c.3612_3618+5del12 variant results from a deletion of 12 nucleotides at the splice junction boundary of coding exon 23 and intron 23 of the RAD50 gene. The deleted nucleotide region is well conserved in available vertebrate species. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |
| Fulgent Genetics, |
RCV002496766 | SCV002782172 | likely pathogenic | Nijmegen breakage syndrome-like disorder | 2022-04-27 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV002496766 | SCV004209732 | likely pathogenic | Nijmegen breakage syndrome-like disorder | 2021-08-31 | criteria provided, single submitter | clinical testing |