rs3026160

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_StrongBP7BA1

The NM_000834.5(GRIN2B):c.2514C>T(p.Cys838Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,670 control chromosomes in the GnomAD database, including 12,498 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.081 ( 689 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11809 hom. )

Consequence

GRIN2B
NM_000834.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.648

Publications

23 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:

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=-0.75).

BP6

Variant 12-13567109-G-A is Benign according to our data. Variant chr12-13567109-G-A is described in ClinVar as Benign. ClinVar VariationId is 129202.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.648 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2B	NM_000834.5 link	c.2514C>T	p.Cys838Cys	synonymous_variant	Exon 13 of 14	ENST00000609686.4	NP_000825.2	Q13224A0A8D9PHB2
GRIN2B	NM_001413992.1 link	c.2514C>T	p.Cys838Cys	synonymous_variant	Exon 14 of 15		NP_001400921.1
GRIN2B	XM_005253351.3 link	c.300C>T	p.Cys100Cys	synonymous_variant	Exon 3 of 4		XP_005253408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4 link	c.2514C>T	p.Cys838Cys	synonymous_variant	Exon 13 of 14	1	NM_000834.5	ENSP00000477455.1		Q13224

Frequencies

GnomAD3 genomes

AF:

0.0807

AC:

12285

AN:

152160

Hom.:

689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0226

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0558

Gnomad ASJ

AF:

0.0786

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0628

Gnomad FIN

AF:

0.0890

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.129

Gnomad OTH

AF:

0.0685

GnomAD2 exomes

AF:

0.0858

AC:

21581

AN:

251480

AF XY:

0.0892

show subpopulations

Gnomad AFR exome

AF:

0.0195

Gnomad AMR exome

AF:

0.0416

Gnomad ASJ exome

AF:

0.0727

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0860

Gnomad NFE exome

AF:

0.128

Gnomad OTH exome

AF:

0.0971

GnomAD4 exome

AF:

0.120

AC:

174886

AN:

1461392

Hom.:

11809

Cov.:

AF XY:

0.118

AC XY:

85758

AN XY:

727028

show subpopulations

African (AFR)

AF:

0.0178

AC:

597

AN:

33480

American (AMR)

AF:

0.0443

AC:

1982

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0757

AC:

1979

AN:

26136

East Asian (EAS)

AF:

0.000378

AC:

AN:

39700

South Asian (SAS)

AF:

0.0686

AC:

5914

AN:

86252

European-Finnish (FIN)

AF:

0.0893

AC:

4773

AN:

53420

Middle Eastern (MID)

AF:

0.0555

AC:

320

AN:

5766

European-Non Finnish (NFE)

AF:

0.138

AC:

153039

AN:

1111526

Other (OTH)

AF:

0.104

AC:

6267

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

7779

15558

23336

31115

38894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5424

10848

16272

21696

27120

<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:

0.0807

AC:

12285

AN:

152278

Hom.:

689

Cov.:

AF XY:

0.0766

AC XY:

5702

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0226

AC:

938

AN:

41568

American (AMR)

AF:

0.0557

AC:

852

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0786

AC:

273

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5184

South Asian (SAS)

AF:

0.0633

AC:

305

AN:

4820

European-Finnish (FIN)

AF:

0.0890

AC:

945

AN:

10616

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.129

AC:

8751

AN:

68006

Other (OTH)

AF:

0.0678

AC:

143

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

575

1150

1725

2300

2875

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<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:

0.0919

Hom.:

2225

Bravo

AF:

0.0764

Asia WGS

AF:

0.0290

AC:

104

AN:

3478

EpiCase

AF:

0.118

EpiControl

AF:

0.122

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 21, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Inborn genetic diseases

Benign:1

Mar 19, 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 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

7.7

(source)

DANN

Benign

0.46

PhyloP100

-0.65

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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