Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000197487 | SCV000254882 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-01-19 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 11 of the RAD50 gene. It does not directly change the encoded amino acid sequence of the RAD50 protein. RNA analysis indicates that this variant 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: 216621). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant 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 | RCV000197487 | SCV000663674 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-18 | criteria provided, single submitter | clinical testing | The c.1793+4A>C intronic variant results from an A to C substitution 4 nucleotides after coding exon 11 in the RAD50 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may result in the creation or strengthening of a novel splice donor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |