ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.3475+2T>C

dbSNP: rs761168506
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000223053 SCV000276583 likely pathogenic Hereditary cancer-predisposing syndrome 2021-04-20 criteria provided, single submitter clinical testing The c.3475+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 22 in the RAD50 gene. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive; however, direct 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. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Invitae RCV000223053 SCV000829454 likely pathogenic Hereditary cancer-predisposing syndrome 2023-10-28 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 22 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 present in population databases (rs761168506, 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: 232444). 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.
Revvity Omics, Revvity RCV001782710 SCV002019599 pathogenic Nijmegen breakage syndrome-like disorder 2019-04-26 criteria provided, single submitter clinical testing

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