Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
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. |
Gene |
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, |
RCV000501673 | SCV000965731 | likely pathogenic | DYRK1A-related intellectual disability syndrome | 2016-01-01 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
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. |
Ce |
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. |
Genome |
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. |