ClinVar Miner

Submissions for variant NM_001347721.2(DYRK1A):c.1010C>T (p.Ser337Phe) (rs1555985649)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000601140 SCV000712522 likely pathogenic Mental retardation, autosomal dominant 7 2016-10-19 criteria provided, single submitter clinical testing The p.Ser346Phe variant in DYRK1A was absent from large population studies and h as been detected in one individual with a range of phenotypic manifestations inc luding intellectual disability, seizures and microcephaly (TIDEX study, pers.com m.) It reportedly was not detected in the unaffected parents, which increases th e likelihood that it is pathogenic. A different amino acid change at the same po sition (p.Ser346Pro) has been identified as a de novo variant in 2 individuals w ith intellectual disability, autism, and microcephaly (Bronicki 2015, DDDS 2015) , further supporting that a change at this position may not be tolerated. This i s consistent with computational predictions that suggest an impact to the protei n. Finally, the DYRK1A gene is associated with "DYRK1A-related intellectual disa bility syndrome with all cases reported to date resulting from a de novo variant (https://www.ncbi.nlm.nih.gov/books/NBK333438/). In summary, the available evi dence suggests that the Ser346Phe variant is likely pathogenic.

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