NM_001347721.2(DYRK1A):c.556G>A (p.Ala186Thr) AND DYRK1A-related intellectual disability syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 2, 2021
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:: RCV001948932.4

Allele description [Variation Report for NM_001347721.2(DYRK1A):c.556G>A (p.Ala186Thr)]

NM_001347721.2(DYRK1A):c.556G>A (p.Ala186Thr)

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.556G>A (p.Ala186Thr)

HGVS:

NC_000021.9:g.37486533G>A
NG_009366.1:g.123977G>A
NM_001347721.2:c.556G>AMANE SELECT
NM_001347722.2:c.556G>A
NM_001347723.2:c.469G>A
NM_001396.5:c.583G>A
NM_101395.2:c.583G>A
NM_130436.2:c.556G>A
NM_130438.2:c.583G>A
NP_001334650.1:p.Ala186Thr
NP_001334651.1:p.Ala186Thr
NP_001334652.1:p.Ala157Thr
NP_001387.2:p.Ala195Thr
NP_567824.1:p.Ala195Thr
NP_569120.1:p.Ala186Thr
NP_569122.1:p.Ala195Thr
NC_000021.8:g.38858835G>A

Protein change:

A157T

Links:

dbSNP: rs2148600841

NCBI 1000 Genomes Browser:

rs2148600841

Molecular consequence:

NM_001347721.2:c.556G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001347722.2:c.556G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001347723.2:c.469G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001396.5:c.583G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_101395.2:c.583G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130436.2:c.556G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_130438.2:c.583G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002213284	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 2, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28167836, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002213284

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 2, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Autism-associated Dyrk1a truncation mutants impair neuronal dendritic and spine growth and interfere with postnatal cortical development.

Dang T, Duan WY, Yu B, Tong DL, Cheng C, Zhang YF, Wu W, Ye K, Zhang WX, Wu M, Wu BB, An Y, Qiu ZL, Wu BL.

Mol Psychiatry. 2018 Mar;23(3):747-758. doi: 10.1038/mp.2016.253. Epub 2017 Feb 7.

PubMed [citation]

PMID:: 28167836
PMCID:: PMC5822466

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002213284.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on DYRK1A function (PMID: 28167836). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DYRK1A protein function. This missense change has been observed in individual(s) with DYRK1A-related conditions (PMID: 28167836). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 195 of the DYRK1A protein (p.Ala195Thr).

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

Last Updated: Sep 29, 2024

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