ClinVar Miner

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

dbSNP: rs1555984461
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Total submissions: 8
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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 DYRK1A-related intellectual disability syndrome 2017-02-16 criteria provided, single submitter clinical testing
Invitae RCV000501673 SCV000660433 pathogenic DYRK1A-related intellectual disability syndrome 2020-01-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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. 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). This variant is not present in population databases (ExAC no frequency). 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.
GeneDx RCV000599528 SCV000709803 pathogenic not provided 2023-01-05 criteria provided, single submitter clinical testing Functional studies demonstrate abnormal gene splicing with skipping of exon 6 (Luco et al., 2016); In silico analysis supports a deleterious effect on splicing; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26922654, 27241786, 34345024, 33562844, 33004838, 35709690)
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000501673 SCV000965731 likely pathogenic DYRK1A-related intellectual disability syndrome 2016-01-01 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV000501673 SCV001370159 likely pathogenic DYRK1A-related intellectual disability syndrome 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.
CeGaT Center for Human Genetics Tuebingen RCV000599528 SCV001962416 pathogenic not provided 2021-08-01 criteria provided, single submitter clinical testing
3billion RCV000501673 SCV003842142 pathogenic DYRK1A-related intellectual disability syndrome 2023-02-23 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. This variant was predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been previously reported as de novo in a similarly affected individual (PMID: 26922654). The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000435011 / PMID: 26922654 / 3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
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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