NM_021956.5(GRIK2):c.1979C>G (p.Thr660Arg) AND Neurodevelopmental disorder with impaired language and ataxia and with or without seizures

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 28, 2021
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV001751791.2

Allele description [Variation Report for NM_021956.5(GRIK2):c.1979C>G (p.Thr660Arg)]

NM_021956.5(GRIK2):c.1979C>G (p.Thr660Arg)

Gene:

GRIK2:glutamate ionotropic receptor kainate type subunit 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6q16.3

Genomic location:

Preferred name:

NM_021956.5(GRIK2):c.1979C>G (p.Thr660Arg)

HGVS:

NC_000006.12:g.101928526C>G
NG_009224.2:g.534497C>G
NM_001166247.1:c.1979C>G
NM_021956.5:c.1979C>GMANE SELECT
NM_175768.3:c.1979C>G
NP_001159719.1:p.Thr660Arg
NP_068775.1:p.Thr660Arg
NP_786944.1:p.Thr660Arg
NC_000006.11:g.102376401C>G

Protein change:

T660R; THR660ARG

Links:

OMIM: 138244.0005; dbSNP: rs1790058081

NCBI 1000 Genomes Browser:

rs1790058081

Molecular consequence:

NM_001166247.1:c.1979C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_021956.5:c.1979C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_175768.3:c.1979C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neurodevelopmental disorder with impaired language and ataxia and with or without seizures
Identifiers:: MONDO: MONDO:0859201; MedGen: C5562006; OMIM: 619580

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001985066	OMIM	no assertion criteria provided	Pathogenic (Oct 28, 2021)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001985066

OMIM

no assertion criteria provided

Pathogenic
(Oct 28, 2021)

germline

literature only

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Clustered mutations in the GRIK2 kainate receptor subunit gene underlie diverse neurodevelopmental disorders.

Stolz JR, Foote KM, Veenstra-Knol HE, Pfundt R, Ten Broeke SW, de Leeuw N, Roht L, Pajusalu S, Part R, Rebane I, Õunap K, Stark Z, Kirk EP, Lawson JA, Lunke S, Christodoulou J, Louie RJ, Rogers RC, Davis JM, Innes AM, Wei XC, Keren B, et al.

Am J Hum Genet. 2021 Sep 2;108(9):1692-1709. doi: 10.1016/j.ajhg.2021.07.007. Epub 2021 Aug 9. Erratum in: Am J Hum Genet. 2021 Nov 4;108(11):2206. doi: 10.1016/j.ajhg.2021.09.018.

PubMed [citation]

PMID:: 34375587
PMCID:: PMC8456161

Details of each submission

From OMIM, SCV001985066.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 2 unrelated patients with neurodevelopmental disorder with impaired language, ataxia, and seizures (NEDLAS; 619580), Stolz et al. (2021) identified a de novo heterozygous c.1979C-G transversion (chr6.102,376,401C-G, GRCh38) in the GRIK2 gene, resulting in a thr660-to-arg (T660R) substitution at a conserved residue in the M3 transmembrane domain. The mutation, which was found by exome sequencing, was not present in the gnomAD database. In vitro functional expression studies indicated that the mutation caused profound slowing of channel deactivation and constitutive tonic current activation compared to wildtype, indicating altered channel gating kinetics.

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

Last Updated: Dec 24, 2023

ClinVar

Relating variation to medicine