ClinVar Miner

Submissions for variant NM_001347721.2(DYRK1A):c.664C>T (p.Arg222Ter) (rs780441716)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481862 SCV000573208 pathogenic not provided 2018-02-06 criteria provided, single submitter clinical testing The R231X nonsense variant in the DYRK1A gene has been reported previously as a de novo variant in an individual with microcephaly, brachycephaly, pulmonary valve abnormality, iris coloboma, micrognathia, eczema, constipation, and short stature (Fitzgerald et al., 2015). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R231X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R231X as a pathogenic variant.
Ambry Genetics RCV000622466 SCV000741114 pathogenic Inborn genetic diseases 2015-10-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Invitae RCV000698811 SCV000827498 pathogenic Mental retardation, autosomal dominant 7 2018-06-01 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg231*) in the DYRK1A gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been reported to be de novo in the literature in an individual with a neurodevelopmental disorder and multiple congenital anomalies (PMID: 28053047). ClinVar contains an entry for this variant (Variation ID: 423502). Loss-of-function variants in DYRK1A are known to be pathogenic (PMID: 25944381). For these reasons, this variant has been classified as Pathogenic.

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