ClinVar Miner

Submissions for variant NM_001347721.2(DYRK1A):c.1372C>T (p.Arg458Ter)

dbSNP: rs797044520
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UCLA Clinical Genomics Center, UCLA RCV000190479 SCV000206787 pathogenic DYRK1A-related intellectual disability syndrome 2014-09-15 criteria provided, single submitter clinical testing
Baylor Genetics RCV000190479 SCV000245476 pathogenic DYRK1A-related intellectual disability syndrome 2012-10-28 criteria provided, single submitter clinical testing This nonsense variant is categorized as deleterious according to ACMG guidelines (PMID:18414213) and was found once in our laboratory de novo in an 18-year-old male with austistic spectrum, moderate intellectual disability, hypotonia, spasticity and ataxia, knee contractures, seizures, dysmorphisms, tall stature, hallux valgus, microcephaly, optic nerve pallor, orchiopexy/inguinal hernia repaired, dermoid or pilomatrixoma spontaneously resolved
GeneDx RCV000522958 SCV000618033 pathogenic not provided 2022-10-03 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34345024, 26633545, 31263215, 25944381, 31216405, 30831192)
Genomic Medicine Lab, University of California San Francisco RCV000190479 SCV001573040 pathogenic DYRK1A-related intellectual disability syndrome 2020-08-27 criteria provided, single submitter clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV001731507 SCV001984778 pathogenic DYRK1A-related disorder criteria provided, single submitter clinical testing This nonsense variant occurs in exon 9 of 11 and is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously identified in multiple individuals with developmental regression, microcephaly, intellectual disability, global developmental delay, severe speech delay, seizures, feeding difficulties, and autism spectrum disorder (PMID: 26677511, 30831192, 25944381). Loss-of-function variation is an established mechanism of disease for DYRK1A-related disorders (PMID: 26677511). The c.1399C>T (p.Arg467Ter) variant is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.1399C>T (p.Arg467Ter) variant is classified as Pathogenic.
Genomic Medicine Lab, University of California San Francisco RCV000190479 SCV002576348 pathogenic DYRK1A-related intellectual disability syndrome criteria provided, single submitter clinical testing
Invitae RCV000190479 SCV003444390 pathogenic DYRK1A-related intellectual disability syndrome 2023-07-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg467*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with DYRK1A-related conditions (PMID: 25944381). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 204005). For these reasons, this variant has been classified as Pathogenic.
Service de Génétique Moléculaire, Hôpital Robert Debré RCV000190479 SCV001432351 pathogenic DYRK1A-related intellectual disability syndrome no assertion criteria provided clinical testing

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