NM_000834.5(GRIN2B):c.448A>G (p.Ile150Val) AND Intellectual disability, autosomal dominant 6

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jun 29, 2023
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:: RCV001172347.2

Allele description [Variation Report for NM_000834.5(GRIN2B):c.448A>G (p.Ile150Val)]

NM_000834.5(GRIN2B):c.448A>G (p.Ile150Val)

Gene:

GRIN2B:glutamate ionotropic receptor NMDA type subunit 2B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p13.1

Genomic location:

Preferred name:

NM_000834.5(GRIN2B):c.448A>G (p.Ile150Val)

HGVS:

NC_000012.12:g.13753879T>C
NG_031854.2:g.233134A>G
NM_000834.5:c.448A>GMANE SELECT
NP_000825.2:p.Ile150Val
NC_000012.11:g.13906813T>C
NM_000834.3:c.448A>G

Protein change:

I150V

Links:

dbSNP: rs796052570

NCBI 1000 Genomes Browser:

rs796052570

Molecular consequence:

NM_000834.5:c.448A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Intellectual disability, autosomal dominant 6 (MRD6)
Synonyms:: INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 6, WITH OR WITHOUT SEIZURES
Identifiers:: MONDO: MONDO:0013509; MedGen: C3151411; OMIM: 613970

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
SCV001335393	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 4, 2017)	de novo	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28377535, 25741868
SCV004175269	Genetics and Molecular Pathology, SA Pathology See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 29, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26633542, 28377535, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001335393

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 4, 2017)

de novo

clinical testing

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

SCV004175269

Genetics and Molecular Pathology, SA Pathology

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 29, 2023)

germline

clinical testing

PubMed (3)
[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	yes	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

Clinical application of whole-exome sequencing across clinical indications.

Retterer K, Juusola J, Cho MT, Vitazka P, Millan F, Gibellini F, Vertino-Bell A, Smaoui N, Neidich J, Monaghan KG, McKnight D, Bai R, Suchy S, Friedman B, Tahiliani J, Pineda-Alvarez D, Richard G, Brandt T, Haverfield E, Chung WK, Bale S.

Genet Med. 2016 Jul;18(7):696-704. doi: 10.1038/gim.2015.148. Epub 2015 Dec 3.

PubMed [citation]

PMID:: 26633542

GRIN2B encephalopathy: novel findings on phenotype, variant clustering, functional consequences and treatment aspects.

Platzer K, Yuan H, Schütz H, Winschel A, Chen W, Hu C, Kusumoto H, Heyne HO, Helbig KL, Tang S, Willing MC, Tinkle BT, Adams DJ, Depienne C, Keren B, Mignot C, Frengen E, Strømme P, Biskup S, Döcker D, Strom TM, Mefford HC, et al.

J Med Genet. 2017 Jul;54(7):460-470. doi: 10.1136/jmedgenet-2016-104509. Epub 2017 Apr 4.

PubMed [citation]

PMID:: 28377535
PMCID:: PMC5656050

See all PubMed Citations (3)

Details of each submission

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001335393.1

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

Description

This variant was identified as de novo (maternity and paternity confirmed).

#	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 Genetics and Molecular Pathology, SA Pathology, SCV004175269.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The GRIN2B c.448A>G variant is classified as LIKELY PATHOGENIC (PS4_Supporting, PS2, PM2) The GRIN2B c.448A>G variant is a single nucleotide change in exon 4/14 of the GRIN2B gene, which is predicted to change the amino acid isoleucine at position 150 in the protein to valine. This variant has been identified as a de novo variant in this patient as well as in one reported case (PMID:28377535) (PS2), and has also been reported in other individuals with intellectual disability (PMID:26633542) (PS4_supporting). This variant is absent from population databases (PM2). The variant has been reported in dbSNP (rs796052570) and in the HGMD database: CM1618931. It has been reported as likely pathogenic by other diagnostic laboratories (ClinVar Variation ID: 205709).

#	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: Mar 5, 2025

ClinVar

Relating variation to medicine