Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000566085 | SCV000663701 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-05-26 | criteria provided, single submitter | clinical testing | The c.1794-1G>A intronic variant results from a G to A substitution one nucleotide upstream from coding exon 12 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 experimental 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. |
Labcorp Genetics |
RCV000566085 | SCV001231869 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-09-05 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 11 of the RAD50 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or altered protein product. This variant is present in population databases (rs587781742, gnomAD 0.003%). 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: 480451). Studies have shown that disruption of this splice site results in activation of a cryptic splice site, and produces a non-functional protein and/or introduces a premature termination codon (internal data). For these reasons, this variant has been classified as Pathogenic. |
Sema4, |
RCV002257845 | SCV002538460 | likely pathogenic | Nijmegen breakage syndrome-like disorder | 2021-05-18 | criteria provided, single submitter | curation | |
Baylor Genetics | RCV002257845 | SCV004207444 | likely pathogenic | Nijmegen breakage syndrome-like disorder | 2022-04-07 | criteria provided, single submitter | clinical testing |