NM_001347721.2(DYRK1A):c.760C>T (p.Arg254Ter) AND DYRK1A-related intellectual disability syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 4, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV003126661.3

Allele description [Variation Report for NM_001347721.2(DYRK1A):c.760C>T (p.Arg254Ter)]

NM_001347721.2(DYRK1A):c.760C>T (p.Arg254Ter)

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.760C>T (p.Arg254Ter)

HGVS:

NC_000021.9:g.37490297C>T
NG_009366.1:g.127741C>T
NM_001347721.2:c.760C>TMANE SELECT
NM_001347722.2:c.760C>T
NM_001347723.2:c.673C>T
NM_001396.5:c.787C>T
NM_101395.2:c.787C>T
NM_130436.2:c.760C>T
NM_130438.2:c.787C>T
NP_001334650.1:p.Arg254Ter
NP_001334651.1:p.Arg254Ter
NP_001334652.1:p.Arg225Ter
NP_001387.2:p.Arg263Ter
NP_001387.2:p.Arg263Ter
NP_567824.1:p.Arg263Ter
NP_569120.1:p.Arg254Ter
NP_569122.1:p.Arg263Ter
NC_000021.8:g.38862599C>T
NM_001396.3:c.787C>T
NM_001396.4:c.787C>T

Protein change:

R225*

Links:

dbSNP: rs886041291

NCBI 1000 Genomes Browser:

rs886041291

Molecular consequence:

NM_001347721.2:c.760C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001347722.2:c.760C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001347723.2:c.673C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001396.5:c.787C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_101395.2:c.787C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130436.2:c.760C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_130438.2:c.787C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: DYRK1A-related intellectual disability syndrome (MRD7)
Synonyms:: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 7
Identifiers:: MONDO: MONDO:0013578; MedGen: C5568143; OMIM: 614104

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003803826	Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 4, 2020)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004801512	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSLVariantClassificationCriteria RUGD 01 April 2020)	Pathogenic (Feb 13, 2018)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003803826

Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 4, 2020)

de novo

clinical testing

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

SCV004801512

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSLVariantClassificationCriteria RUGD 01 April 2020)

Pathogenic
(Feb 13, 2018)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	de novo	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 Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine, SCV003803826.1

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

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

From Illumina Laboratory Services, Illumina, SCV004801512.1

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

Description

The DYRK1A c.787C>T (p.Arg263Ter) stop-gained variant has been reported in two patients in the literature in a de novo state (Luco et al. 2016; Evers et al. 2017). Both patients had intellectual disability, microcephaly (post-natal onset specified for at least one patient), developmental delay and deeply set eyes in common. Control data are unavailable for this variant. This variant is absent from the Genome Aggregation Database. Based on the available evidence, the c.787C>T (p.Arg263Ter) variant is classified as pathogenic for DYRK1A-related intellectual disability syndrome.

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

Last Updated: Oct 20, 2024

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