Submissions for variant NM_001347721.2(DYRK1A):c.1753C>T (p.Gln585Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002894388	SCV003236884	pathogenic	DYRK1A-related intellectual disability syndrome	2022-10-15	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the DYRK1A protein in which other variant(s) (p.Ser641Rfs*31) have been determined to be pathogenic (PMID: 35598272). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This premature translational stop signal has been observed in individual(s) with clinical features of DYRK1A-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln594*) in the DYRK1A gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 170 amino acid(s) of the DYRK1A protein.
PreventionGenetics, part of Exact Sciences	RCV004536425	SCV004119700	likely pathogenic	DYRK1A-related disorder	2022-11-30	criteria provided, single submitter	clinical testing	The DYRK1A c.1780C>T variant is predicted to result in premature protein termination (p.Gln594*). This variant is located in the last exon of DYRK1A and is not predicted to result in nonsense mediated decay. However, this variant truncates the final 170 amino acids and other de novo truncating variants have been reported downstream of this variant in individuals with intellectual disability (Human Gene Mutation Database). To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Nonsense variants in DYRK1A are expected to be pathogenic. This variant is interpreted as likely pathogenic.