rs1806201

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000834.5(GRIN2B):c.2664C>T(p.Thr888Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,613,394 control chromosomes in the GnomAD database, including 69,306 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5287 hom., cov: 32)

Exomes 𝑓: 0.29 ( 64019 hom. )

Consequence

GRIN2B
NM_000834.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -1.59

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 12-13564574-G-A is Benign according to our data. Variant chr12-13564574-G-A is described in ClinVar as [Benign]. Clinvar id is 98437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-13564574-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-1.59 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRIN2B	NM_000834.5 link	c.2664C>T	p.Thr888Thr	synonymous_variant	Exon 14 of 14	ENST00000609686.4	NP_000825.2	Q13224A0A8D9PHB2
GRIN2B	NM_001413992.1 link	c.2664C>T	p.Thr888Thr	synonymous_variant	Exon 15 of 15		NP_001400921.1
GRIN2B	XM_005253351.3 link	c.450C>T	p.Thr150Thr	synonymous_variant	Exon 4 of 4		XP_005253408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRIN2B	ENST00000609686.4 link	c.2664C>T	p.Thr888Thr	synonymous_variant	Exon 14 of 14	1	NM_000834.5	ENSP00000477455.1		Q13224
GRIN2B	ENST00000637214.1 link	c.69+44029C>T		intron_variant	Intron 1 of 1	5		ENSP00000489997.1		A0A1B0GU78

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37346

AN:

151914

Hom.:

5282

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.291

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.509

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.215

Gnomad NFE

AF:

0.268

Gnomad OTH

AF:

0.261

GnomAD3 exomes

AF:

0.316

AC:

79410

AN:

251050

Hom.:

13861

AF XY:

0.320

AC XY:

43456

AN XY:

135746

show subpopulations

Gnomad AFR exome

AF:

0.0991

Gnomad AMR exome

AF:

0.329

Gnomad ASJ exome

AF:

0.333

Gnomad EAS exome

AF:

0.523

Gnomad SAS exome

AF:

0.417

Gnomad FIN exome

AF:

0.372

Gnomad NFE exome

AF:

0.271

Gnomad OTH exome

AF:

0.311

GnomAD4 exome

AF:

0.289

AC:

421632

AN:

1461362

Hom.:

64019

Cov.:

AF XY:

0.292

AC XY:

212222

AN XY:

727022

show subpopulations

Gnomad4 AFR exome

AF:

0.0967

Gnomad4 AMR exome

AF:

0.323

Gnomad4 ASJ exome

AF:

0.335

Gnomad4 EAS exome

AF:

0.495

Gnomad4 SAS exome

AF:

0.409

Gnomad4 FIN exome

AF:

0.365

Gnomad4 NFE exome

AF:

0.271

Gnomad4 OTH exome

AF:

0.295

GnomAD4 genome

AF:

0.246

AC:

37355

AN:

152032

Hom.:

5287

Cov.:

AF XY:

0.256

AC XY:

19005

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.286

Gnomad4 ASJ

AF:

0.332

Gnomad4 EAS

AF:

0.509

Gnomad4 SAS

AF:

0.401

Gnomad4 FIN

AF:

0.367

Gnomad4 NFE

AF:

0.268

Gnomad4 OTH

AF:

0.265

Alfa

AF:

0.256

Hom.:

4567

Bravo

AF:

0.235

Asia WGS

AF:

0.432

AC:

1499

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 47% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 44. Only high quality variants are reported. -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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. -

not provided

Benign:3Other:1

Psychiatry Genetics Yale University

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Apr 20, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24292895, 17569088) -

Inborn genetic diseases

Benign:1

Jan 08, 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

-0.79

CADD

Benign

6.1

DANN

Benign

0.71

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over