Submissions for variant NM_001347721.2(DYRK1A):c.322C>T (p.Arg108Ter)

dbSNP: rs1057518204

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413934	SCV000491650	pathogenic	not provided	2021-12-16	criteria provided, single submitter	clinical testing	Reported previously in an individual with seizures and intellectual disability; however additional details were not provided (Helbig et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 28191889, 33562844, 33004838, 26795593)
Genetic Services Laboratory, University of Chicago	RCV000499667	SCV000594471	pathogenic	DYRK1A-related intellectual disability syndrome	2016-10-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000623331	SCV000740863	pathogenic	Inborn genetic diseases	2015-03-27	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000413934	SCV001246784	pathogenic	not provided	2019-11-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000499667	SCV002181783	pathogenic	DYRK1A-related intellectual disability syndrome	2023-12-01	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg117*) in the DYRK1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DYRK1A are known to be pathogenic (PMID: 25944381). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with clinical features of DYRK1A-related conditions (PMID: 26795593, 28191889, 33004838). ClinVar contains an entry for this variant (Variation ID: 373087). For these reasons, this variant has been classified as Pathogenic.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV000499667	SCV002559158	pathogenic	DYRK1A-related intellectual disability syndrome		criteria provided, single submitter	clinical testing
Laboratory Cellgenetics, GMDL Cellgenetics	RCV000499667	SCV004697449	pathogenic	DYRK1A-related intellectual disability syndrome		criteria provided, single submitter	clinical testing
GenomeConnect - Simons Searchlight	RCV001265465	SCV001443600	pathogenic	Complex neurodevelopmental disorder	2017-08-25	no assertion criteria provided	provider interpretation	Submission from Simons Searchlight facilitated by GenomeConnect. Variant interpreted by the Simons Searchlight team most recently on 2017-08-25 and interpreted as Pathogenic. Variant was initially reported on 2017-07-05 by GTR ID of laboratory name 26957. The reporting laboratory might also submit to ClinVar.