Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000795046 | SCV000934486 | uncertain significance | DYRK1A-related intellectual disability syndrome | 2023-12-09 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 709 of the DYRK1A protein (p.Arg709Cys). This variant is present in population databases (rs781697806, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with DYRK1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 641739). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
New York Genome Center | RCV001281504 | SCV001468813 | uncertain significance | Seizure | 2019-05-30 | criteria provided, single submitter | clinical testing | The c.2125C>T (p.Arg709Cys) variant identified in the DYRK1A gene substitutes a highly conserved Arginine for Cysteine at amino acid 709/764 (coding exon 12/12). It is found with low frequency in gnomAD (2 heterozygotes, 0 homozygotes; allele frequency:7.953e-6) and ExAC (1 heterozygote, 0 homozygotes; allele frequency: 8.23e-6), suggesting it is not a common benign variant in the populations represented in these dataases. In silico algorithms do not agree on the affect of this variant on the function of the canonical transcript, as it is predicted both Neutral (Provean; score: -1.14) and Damaging (SIFT; score:0.000). This variant is absent from ClinVar and to our current knowledge has not been identified in affected individuals in the literature. Given the lack of compelling information regarding the pathogenicity of this variant, it is reported here as a Varaint of Uncertain Significance. |