Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000576181 | SCV000677027 | pathogenic | DYRK1A-related intellectual disability syndrome | 2022-10-25 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 487250). This variant has been observed in individual(s) with DYRK1A-related disease (PMID: 25707398; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 5 of the DYRK1A gene. It does not directly change the encoded amino acid sequence of the DYRK1A protein. It affects a nucleotide within the consensus splice site. |
Institute for Genomic Medicine |
RCV000576181 | SCV001423647 | likely pathogenic | DYRK1A-related intellectual disability syndrome | 2019-01-18 | criteria provided, single submitter | clinical testing | [ACMG/AMP: PS2, PM2, PP5] This alteration is de novo in origin as it was not detected in the submitted parental specimens (identity confirmed) [PS2], is absent from or rarely observed in large-scale population databases [PM2], was reported as a pathogenic/likely pathogenic alteration by a reputable source (ClinVar or other correspondence from a clinical testing laboratory) [PP5]. |
Diagnostic Laboratory, |
RCV001260680 | SCV001437772 | likely pathogenic | Intellectual disability | 2020-09-10 | criteria provided, single submitter | clinical testing | |
Institute of Medical Genetics and Applied Genomics, |
RCV001268095 | SCV001446747 | pathogenic | not provided | 2020-10-23 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001268095 | SCV002765792 | pathogenic | not provided | 2022-10-31 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 25707398, 28135719, 32371413, 28252636, 31526516, 33562844, 34345024) |
Center for Personalized Medicine, |
RCV003156105 | SCV003845251 | likely pathogenic | See cases | 2022-12-21 | criteria provided, single submitter | clinical testing | |
Victorian Clinical Genetics Services, |
RCV000576181 | SCV003922009 | pathogenic | DYRK1A-related intellectual disability syndrome | 2021-05-07 | criteria provided, single submitter | clinical testing | 0102 - Loss of function is a known mechanism of disease in this gene and is associated with DYRK1A-related intellectual disability syndrome, MONDO: 0013578. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0212 - Non-canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0508 - In silico predictions for abnormal splicing are conflicting. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported as pathogenic multiple times in the ClinVar database, and twice in the literature as de novo in individuals with intellectual disability and other features (PMID: 25707398, 32371413). (SP) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
Service de Génétique Moléculaire, |
RCV000576181 | SCV001432317 | likely pathogenic | DYRK1A-related intellectual disability syndrome | no assertion criteria provided | clinical testing |