Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001017508 | SCV001178597 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-03-15 | criteria provided, single submitter | clinical testing | The c.2922+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 18 of the RAD50 gene. 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 |
RCV001017508 | SCV004694023 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2023-09-03 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 18 of the RAD50 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RAD50 are known to be pathogenic (PMID: 19409520). 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: 822272). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| CZECANCA consortium | RCV001271001 | SCV001451813 | likely pathogenic | Breast and/or ovarian cancer | 2019-06-11 | no assertion criteria provided | clinical testing |