ClinVar Miner

Submissions for variant NM_001356.4(DDX3X):c.874C>T (p.Arg292Ter) (rs1555953488)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519583 SCV000620988 pathogenic not provided 2018-07-06 criteria provided, single submitter clinical testing The R292X variant in the DDX3X gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R292X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret R292X as a pathogenic variant
Ambry Genetics RCV000718415 SCV000849278 pathogenic History of neurodevelopmental disorder 2017-03-31 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Invitae RCV000519583 SCV000939481 pathogenic not provided 2018-10-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg292*) in the DDX3X 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 DDX3X-related disease. ClinVar contains an entry for this variant (Variation ID: 452201). Loss-of-function variants in DDX3X are known to be pathogenic (PMID: 26235985). For these reasons, this variant has been classified as Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV001174975 SCV001338460 likely pathogenic Mental retardation, X-linked 102 2020-04-10 criteria provided, single submitter clinical testing Variant summary: DDX3X c.874C>T (p.Arg292X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 178756 control chromosomes (gnomAD). c.874C>T has been reported in the literature in a female individual affected with X-linked Intellectual Disability (Wang_2018). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001174975 SCV001428217 pathogenic Mental retardation, X-linked 102 2019-01-01 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.