Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000218272 | SCV000274472 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2018-01-19 | criteria provided, single submitter | clinical testing | The c.130-1G>T intronic variant results from a G to T substitution one nucleotide upstream from coding exon 2 of the RAD50 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. 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. |
| Invitae | RCV000218272 | SCV000628149 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-09-04 | criteria provided, single submitter | clinical testing | 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. Studies have shown that disruption of this splice site results in skipping of exon 2, but is expected to preserve the integrity of the reading-frame (Invitae). ClinVar contains an entry for this variant (Variation ID: 230801). Disruption of this splice site has been observed in individual(s) with ovarian cancer (PMID: 33099839). This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change affects an acceptor splice site in intron 1 of the RAD50 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely results in a shortened protein product. |