ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.551+2T>C

dbSNP: rs1580987375
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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 RCV001024210 SCV001186184 likely pathogenic Hereditary cancer-predisposing syndrome 2020-02-25 criteria provided, single submitter clinical testing The c.551+2T>C intronic variant results from a T to C substitution two nucleotides after coding exon 4 in the RAD50 gene. This nucleotide position is highly conserved in available vertebrate species. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Using the BDGP and Human Splicing Finder (HSF) splice site prediction tools, this alteration will abolish the native splice donor site; however, direct evidence is unavailable (Desmet FO et al. Nucleic Acids Res. 2009 May;37:e67). 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.
Invitae RCV001024210 SCV001406117 likely pathogenic Hereditary cancer-predisposing syndrome 2023-01-20 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 825797). 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 affects a donor splice site in intron 4 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).
Revvity Omics, Revvity RCV001784561 SCV002019597 pathogenic Nijmegen breakage syndrome-like disorder 2019-04-11 criteria provided, single submitter clinical testing

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