Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Equipe Genetique des Anomalies du Developpement, |
RCV000824986 | SCV000966166 | likely pathogenic | DYRK1A-related intellectual disability syndrome | 2018-06-26 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000824986 | SCV002243320 | pathogenic | DYRK1A-related intellectual disability syndrome | 2021-08-03 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 8 of the DYRK1A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DYRK1A are known to be pathogenic (PMID: 25944381). This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individual(s) with clinical features of DYRK1A-related conditions (PMID: 25707398, 31130284). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 666564). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Prevention |
RCV003975335 | SCV004787791 | pathogenic | DYRK1A-related condition | 2023-12-19 | criteria provided, single submitter | clinical testing | The DYRK1A c.1240-2A>G variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant has been reported in at least two patients with autism spectrum disorder, intellectual disability, microcephaly, and developmental delay; and, confirmed to occur de novo (van Bon et al. 2016. PubMed ID: 25707398; Table S1, Monies et al. 2019. PubMed ID: 31130284; Table S1, Maddirevula et al. 2020. PubMed ID: 32552793; Courraud et al. 2021. PubMed ID: 34345024). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Variants that disrupt the consensus splice acceptor site in DYRK1A are expected to be pathogenic. This variant is interpreted as pathogenic. |