NM_001347721.2(DYRK1A):c.1372C>T (p.Arg458Ter) AND DYRK1A-related disorder

Germline classification:: Pathogenic (1 submission)
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001731507.1

Allele description [Variation Report for NM_001347721.2(DYRK1A):c.1372C>T (p.Arg458Ter)]

NM_001347721.2(DYRK1A):c.1372C>T (p.Arg458Ter)

Gene:

DYRK1A:dual specificity tyrosine phosphorylation regulated kinase 1A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

21q22.13

Genomic location:

Preferred name:

NM_001347721.2(DYRK1A):c.1372C>T (p.Arg458Ter)

HGVS:

NC_000021.9:g.37505442C>T
NG_009366.1:g.142887C>T
NM_001347721.2:c.1372C>TMANE SELECT
NM_001347722.2:c.1372C>T
NM_001347723.2:c.1285C>T
NM_001396.5:c.1399C>T
NM_101395.2:c.1399C>T
NM_130436.2:c.1372C>T
NM_130438.2:c.1399C>T
NP_001334650.1:p.Arg458Ter
NP_001334651.1:p.Arg458Ter
NP_001334652.1:p.Arg429Ter
NP_001387.2:p.Arg467Ter
NP_567824.1:p.Arg467Ter
NP_569120.1:p.Arg458Ter
NP_569122.1:p.Arg467Ter
NC_000021.8:g.38877745C>T
NM_001396.3:c.1399C>T
p.Arg467*

Protein change:

R429*

Links:

dbSNP: rs797044520

NCBI 1000 Genomes Browser:

rs797044520

Molecular consequence:

NM_001347721.2:c.1372C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001347722.2:c.1372C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001347723.2:c.1285C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001396.5:c.1399C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_101395.2:c.1399C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130436.2:c.1372C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130438.2:c.1399C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: DYRK1A-related disorder
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001984778	Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego - CSER-NYCKidSeq	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001984778

Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego - CSER-NYCKidSeq

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego - CSER-NYCKidSeq, SCV001984778.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This nonsense variant occurs in exon 9 of 11 and is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously identified in multiple individuals with developmental regression, microcephaly, intellectual disability, global developmental delay, severe speech delay, seizures, feeding difficulties, and autism spectrum disorder (PMID: 26677511, 30831192, 25944381). Loss-of-function variation is an established mechanism of disease for DYRK1A-related disorders (PMID: 26677511). The c.1399C>T (p.Arg467Ter) variant is absent from the gnomAD population database and thus is presumed to be rare. Based on the available evidence, the c.1399C>T (p.Arg467Ter) variant is classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 31, 2025

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