Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000482962 | SCV000573105 | likely pathogenic | not provided | 2021-06-20 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533) |
Ambry Genetics | RCV002526665 | SCV003591429 | likely pathogenic | Inborn genetic diseases | 2021-12-18 | criteria provided, single submitter | clinical testing | The c.503G>A (p.G168D) alteration is located in exon 4 (coding exon 4) of the DYRK1A gene. This alteration results from a G to A substitution at nucleotide position 503, causing the glycine (G) at amino acid position 168 to be replaced by an aspartic acid (D). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration was reported de novo in an individual with intellectual disability (Courraud, 2021). This amino acid position is highly conserved in available vertebrate species. This missense alteration is located in a region that has a low rate of benign missense variation (Lek, 2016; Firth, 2009). Functional analysis demonstrated that the p.G168D alteration resulted in a significant decrease in DYRK1A expression as well as an absence of DYRK1A autophosphorylation activity (Courraud, 2021). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as likely pathogenic. |
Diagnostic Laboratory, |
RCV001507306 | SCV001712092 | pathogenic | Intellectual disability | 2021-06-07 | no assertion criteria provided | clinical testing |