rs35025065

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_000834.5(GRIN2B):c.1341C>T(p.Asp447Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00891 in 1,612,414 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0085 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0090 ( 88 hom. )

Consequence

GRIN2B
NM_000834.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 0.223

Publications

9 publications found

Variant links:

Genes affected

GRIN2B (HGNC:4586): (glutamate ionotropic receptor NMDA type subunit 2B) This gene encodes a member of the N-methyl-D-aspartate (NMDA) receptor family within the ionotropic glutamate receptor superfamily. The encoded protein is a subunit of the NMDA receptor ion channel which acts as an agonist binding site for glutamate. The NMDA receptors mediate a slow calcium-permeable component of excitatory synaptic transmission in the central nervous system. The NMDA receptors are heterotetramers of seven genetically encoded, differentially expressed subunits including NR1 (GRIN1), NR2 (GRIN2A, GRIN2B, GRIN2C, or GRIN2D) and NR3 (GRIN3A or GRIN3B). The early expression of this gene in development suggests a role in brain development, circuit formation, synaptic plasticity, and cellular migration and differentiation. Naturally occurring mutations within this gene are associated with neurodevelopmental disorders including autism spectrum disorder, attention deficit hyperactivity disorder, epilepsy, and schizophrenia. [provided by RefSeq, Aug 2017]

GRIN2B Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Ambry Genetics
developmental and epileptic encephalopathy, 27
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
intellectual disability, autosomal dominant 6
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

GRIN2B links:

ENSG00000287928 (HGNC:):

ENSG00000287928 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 12-13615652-G-A is Benign according to our data. Variant chr12-13615652-G-A is described in ClinVar as Benign. ClinVar VariationId is 98440.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.223 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00852 (1296/152108) while in subpopulation NFE AF = 0.0109 (738/67992). AF 95% confidence interval is 0.0102. There are 3 homozygotes in GnomAd4. There are 610 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 1296 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2B	NM_000834.5 link	c.1341C>T	p.Asp447Asp	synonymous_variant	Exon 7 of 14	ENST00000609686.4	NP_000825.2	Q13224A0A8D9PHB2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4 link	c.1341C>T	p.Asp447Asp	synonymous_variant	Exon 7 of 14	1	NM_000834.5	ENSP00000477455.1		Q13224

Frequencies

GnomAD3 genomes

AF:

0.00853

AC:

1296

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00911

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00694

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00416

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.00575

GnomAD2 exomes

AF:

0.00654

AC:

1642

AN:

251026

AF XY:

0.00675

show subpopulations

Gnomad AFR exome

AF:

0.00906

Gnomad AMR exome

AF:

0.00445

Gnomad ASJ exome

AF:

0.00407

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00407

Gnomad NFE exome

AF:

0.00975

Gnomad OTH exome

AF:

0.00637

GnomAD4 exome

AF:

0.00895

AC:

13070

AN:

1460306

Hom.:

Cov.:

AF XY:

0.00880

AC XY:

6394

AN XY:

726620

show subpopulations

African (AFR)

AF:

0.00891

AC:

298

AN:

33446

American (AMR)

AF:

0.00501

AC:

224

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00394

AC:

103

AN:

26126

East Asian (EAS)

AF:

0.000302

AC:

AN:

39680

South Asian (SAS)

AF:

0.00228

AC:

197

AN:

86238

European-Finnish (FIN)

AF:

0.00459

AC:

245

AN:

53406

Middle Eastern (MID)

AF:

0.00260

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0103

AC:

11444

AN:

1110582

Other (OTH)

AF:

0.00882

AC:

532

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

602

1204

1807

2409

3011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

414

828

1242

1656

2070

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00852

AC:

1296

AN:

152108

Hom.:

Cov.:

AF XY:

0.00821

AC XY:

610

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.00908

AC:

377

AN:

41504

American (AMR)

AF:

0.00693

AC:

106

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00260

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00104

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00416

AC:

AN:

10572

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0109

AC:

738

AN:

67992

Other (OTH)

AF:

0.00569

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

133

199

266

332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00931

Hom.:

Bravo

AF:

0.00851

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0121

EpiControl

AF:

0.0103

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 13, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Mar 17, 2014

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 22, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2Other:1

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

GRIN2B: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Psychiatry Genetics Yale University

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Inborn genetic diseases

Benign:1

Feb 24, 2016

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Intellectual disability, autosomal dominant 6;C4015316:Developmental and epileptic encephalopathy, 27

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

GRIN2B-related disorder

Benign:1

May 16, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.9

(source)

DANN

Benign

0.64

PhyloP100

0.22

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over