ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.1174_1177del (p.Gln392fs) (rs1554098250)

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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 RCV000567846 SCV000666999 pathogenic Hereditary cancer-predisposing syndrome 2020-04-27 criteria provided, single submitter clinical testing The c.1174_1177delCAGA pathogenic mutation, located in coding exon 8 of the RAD50 gene, results from a deletion of 4 nucleotides between positions 1174 and 1177, causing a translational frameshift with a predicted alternate stop codon (p.Q392Lfs*8). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781782 SCV000920108 likely pathogenic Nijmegen breakage syndrome-like disorder 2018-01-19 criteria provided, single submitter clinical testing Variant summary: The RAD50 c.1174_1177delCAGA (p.Gln392LeufsX8) variant results in a premature termination codon, predicted to cause a truncated or absent RAD50 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant is absent in 245944 control chromosomes. In addition, one clinical diagnostic laboratory/reputable database classified this variant as pathogenic. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.
Invitae RCV000567846 SCV001235612 pathogenic Hereditary cancer-predisposing syndrome 2020-08-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln392Leufs*8) in the RAD50 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RAD50-related conditions. ClinVar contains an entry for this variant (Variation ID: 482086). Loss-of-function variants in RAD50 are known to be pathogenic (PMID: 16385572, 19409520). For these reasons, this variant has been classified as Pathogenic.

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