Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000164601 | SCV000215261 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-06-14 | criteria provided, single submitter | clinical testing | The c.756+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 5 in the RAD50 gene. This alteration was identified in an individual who underwent hereditary cancer multi-gene panel testing (LaDuca H et al. Genet. Med., 2014 Nov;16:830-7). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). 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 |
RCV000164601 | SCV000289075 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-04-22 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 5 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 present in population databases (rs764122619, 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: 185222). Studies have shown that disruption of this splice site results in skipping of exon 5 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. |
| Ce |
RCV001726014 | SCV001961901 | likely pathogenic | not provided | 2021-08-01 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003467299 | SCV004207374 | likely pathogenic | Nijmegen breakage syndrome-like disorder | 2023-07-06 | criteria provided, single submitter | clinical testing | |
| Center for Genomic Medicine, |
RCV001726014 | SCV005873286 | likely pathogenic | not provided | 2025-03-04 | criteria provided, single submitter | clinical testing | Classification criteria: PVS1, PM2_Supporting |