ClinVar Miner

Submissions for variant NM_001347721.2(DYRK1A):c.736C>T (p.Arg246Ter)

dbSNP: rs724159948
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000503841 SCV000594473 pathogenic DYRK1A-related intellectual disability syndrome 2016-06-30 criteria provided, single submitter clinical testing
Invitae RCV000503841 SCV000833797 pathogenic DYRK1A-related intellectual disability syndrome 2022-11-16 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 162152). This premature translational stop signal has been observed in individual(s) with developmental disorders, including intellectual disability and autism (PMID: 25920557, 28053047, 29034068). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg255*) in the DYRK1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYRK1A are known to be pathogenic (PMID: 25944381).
GeneDx RCV000760477 SCV000890366 pathogenic not provided 2018-10-24 criteria provided, single submitter clinical testing The R255X variant in the DYRK1A gene has been reported previously as de novo in an individual with microcephaly, intellectual disability, autism, seizures, and dysmorphic features (Bronicki et al., 2015). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R255X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R255X as a pathogenic variant
CeGaT Center for Human Genetics Tuebingen RCV000760477 SCV001502416 pathogenic not provided 2020-07-01 criteria provided, single submitter clinical testing
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine RCV003126545 SCV003804064 pathogenic Autism spectrum disorder criteria provided, single submitter clinical testing
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV000503841 SCV004176378 pathogenic DYRK1A-related intellectual disability syndrome 2023-02-14 criteria provided, single submitter clinical testing The stop gained c.736C>T(p.Arg246Ter) variant in DYRK1A gene has been reported previously as de novo in individual(s) affected with developmental disorders, including intellectual disability and autism (Earl RK, et. al., 2017; Bronicki LM, et. al., 2015). The c.736C>T variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic (multiple submissions). The nucleotide change c.736C>T in DYRK1A is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This sequence change creates a premature translational stop signal (p.Arg255Ter) in the DYRK1A gene. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants in DYRK1A gene have been previously reported to be disease causing (Ji J, et. al., 2015). For these reasons, this variant has been classified as Pathogenic. This variant in DYRK1A gene is absent in both the parents, hence, confirming that this is a de-novo variant.
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV000149558 SCV000196057 pathogenic Seizure; Feeding difficulties; Deeply set eye; Microcephaly; Intellectual disability; Absent or delayed speech development 2014-09-09 no assertion criteria provided research
Service de Génétique Moléculaire, Hôpital Robert Debré RCV000503841 SCV001432353 pathogenic DYRK1A-related intellectual disability syndrome no assertion criteria provided clinical testing
Diagnostic Laboratory, Strasbourg University Hospital RCV001507325 SCV001712097 pathogenic Intellectual disability 2019-06-19 no assertion criteria provided clinical testing

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