Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000567131 | SCV000663736 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-21 | criteria provided, single submitter | clinical testing | The c.1635+3A>G intronic variant results from an A to G substitution 3 nucleotides after coding exon 10 in the RAD50 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in a transcript predicted to lead to a protein with an in-frame deletion of 61 amino acid(s); however, the exact functional impact of the deleted amino acid(s) is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV000567131 | SCV000753308 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-19 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 480478). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 10, but is expected to preserve the integrity of the reading-frame (Invitae). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 10 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 likely results in a shortened protein product. |