Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000632224 | SCV000753366 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-12-07 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 10 of the RAD50 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). 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: 527365). Studies have shown that disruption of this splice site results in skipping of exon 11 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV000632224 | SCV002704514 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-02-12 | criteria provided, single submitter | clinical testing | The c.1636-2A>G intronic variant results from an A to G substitution two nucleotides upstream from coding exon 11 in 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. |