ClinVar Miner

Submissions for variant NM_001347721.2(DYRK1A):c.208-28G>A (rs552103257)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000658192 SCV000779963 uncertain significance not provided 2018-05-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DYRK1A gene. The c.208-1 G>A varianthas been reported previously in individuals with autism or autism-like disorders (van Bon et al, 2015;Yuen et al., 2017). The c.208-1 G>A variant is observed in 1/111466 (0.001%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). Several in silico spliceprediction models predict that c.208-1 G>A destroys the canonical splice acceptor site of intron 2 and leads to abnormal gene splicing. However, functional analysis of the cDNA suggests that this variant does not affect splicing or function of DYRK1A, as intact copies of both long and short isoforms are retained (van Bon et al., 2015). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
GeneReviews RCV000202627 SCV000257566 benign Mental retardation, autosomal dominant 7 2015-09-30 no assertion criteria provided literature only
Genetic Services Laboratory, University of Chicago RCV000500398 SCV000594480 likely benign not specified 2017-04-12 criteria provided, single submitter clinical testing
Invitae RCV000202627 SCV000835911 uncertain significance Mental retardation, autosomal dominant 7 2018-02-23 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 2 of the DYRK1A gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual with sub-clinical autism spectrum disorder, and was inherited from an unaffected individual (PMID: 25707398). ClinVar contains an entry for this variant (Variation ID: 218379). Experimental studies have shown that this splice acceptor change does not affect all of the DYRK1A mRNA isoforms (PMID: 25707398). 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.

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