ClinVar Miner

Submissions for variant NM_001347721.2(DYRK1A):c.924+4_924+7del (rs1555984461)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000501673 SCV000594475 likely pathogenic Mental retardation, autosomal dominant 7 2017-02-16 criteria provided, single submitter clinical testing
Invitae RCV000501673 SCV000660433 pathogenic Mental retardation, autosomal dominant 7 2020-01-24 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the DYRK1A gene. It does not directly change the encoded amino acid sequence of the DYRK1A protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been shown to arise de novo in an individual affected with syndromic intellectual disability, with features consistent with a DYRK1A-related disorder (PMID: 26922654, 27241786, Invitae). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). RT-PCR and sequencing of the mRNA derived from the individual with this variant showed exon 7 skipping (PMID: 26922654). Exon 7 is referred to as exon 6 in the literature. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000599528 SCV000709803 pathogenic not provided 2017-12-15 criteria provided, single submitter clinical testing The c.951+4_951+7delAGTA variant in the DYRK1A gene has been reported previously as de novo in an individual with syndromic intellectual disability (Luco et al., 2016). The c.951+4_951+7delAGTA variant causes an intronic deletion and is predicted to destroy the natural splice donor site in intron 6. Functional studies demonstrate abnormal gene splicing with skipping of exon 6 (Luco et al., 2016). The c.951+4_951+7delAGTA variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.951+4_951+7delAGTA as a pathogenic variant.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000501673 SCV000965731 likely pathogenic Mental retardation, autosomal dominant 7 2016-01-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000501673 SCV001370159 likely pathogenic Mental retardation, autosomal dominant 7 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PM2.
GenomeConnect - Simons Searchlight RCV001265140 SCV001443175 likely pathogenic Complex neurodevelopmental disorder 2018-12-04 no assertion criteria provided provider interpretation Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2018-12-04 and interpreted as Likely Pathogenic. The reporting laboratory might also submit to ClinVar. This variant was identified in multiple probands enrolled in Simons Searchlight.

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