rs1805522

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_000834.5(GRIN2B):c.1806C>T(p.Ile602=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0484 in 1,613,438 control chromosomes in the GnomAD database, including 2,831 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 262 hom., cov: 32)

Exomes 𝑓: 0.048 ( 2569 hom. )

Consequence

GRIN2B
NM_000834.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.977

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 12-13608807-G-A is Benign according to our data. Variant chr12-13608807-G-A is described in ClinVar as [Benign]. Clinvar id is 129201.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.977 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GRIN2B	NM_000834.5 linkuse as main transcript	c.1806C>T	p.Ile602=	synonymous_variant	10/14	ENST00000609686.4
LOC105369668	XR_001749013.2 linkuse as main transcript	n.342+50G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GRIN2B	ENST00000609686.4 linkuse as main transcript	c.1806C>T	p.Ile602=	synonymous_variant	10/14	1	NM_000834.5	P1
	ENST00000652867.1 linkuse as main transcript	n.203-6291G>A		intron_variant, non_coding_transcript_variant
GRIN2B	ENST00000628166.2 linkuse as main transcript	n.66C>T		non_coding_transcript_exon_variant	2/5	5

Frequencies

GnomAD3 genomes

AF:

0.0512

AC:

7783

AN:

152078

Hom.:

263

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0436

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0562

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.164

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.0809

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0383

Gnomad OTH

AF:

0.0449

GnomAD3 exomes

AF:

0.0652

AC:

16388

AN:

251350

Hom.:

739

AF XY:

0.0658

AC XY:

8936

AN XY:

135836

show subpopulations

Gnomad AFR exome

AF:

0.0429

Gnomad AMR exome

AF:

0.0788

Gnomad ASJ exome

AF:

0.0203

Gnomad EAS exome

AF:

0.152

Gnomad SAS exome

AF:

0.117

Gnomad FIN exome

AF:

0.0784

Gnomad NFE exome

AF:

0.0384

Gnomad OTH exome

AF:

0.0515

GnomAD4 exome

AF:

0.0481

AC:

70319

AN:

1461242

Hom.:

2569

Cov.:

AF XY:

0.0500

AC XY:

36379

AN XY:

726970

show subpopulations

Gnomad4 AFR exome

AF:

0.0481

Gnomad4 AMR exome

AF:

0.0761

Gnomad4 ASJ exome

AF:

0.0199

Gnomad4 EAS exome

AF:

0.183

Gnomad4 SAS exome

AF:

0.115

Gnomad4 FIN exome

AF:

0.0809

Gnomad4 NFE exome

AF:

0.0361

Gnomad4 OTH exome

AF:

0.0494

GnomAD4 genome

AF:

0.0511

AC:

7780

AN:

152196

Hom.:

262

Cov.:

AF XY:

0.0547

AC XY:

4067

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0435

Gnomad4 AMR

AF:

0.0562

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.164

Gnomad4 SAS

AF:

0.131

Gnomad4 FIN

AF:

0.0809

Gnomad4 NFE

AF:

0.0383

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0345

Hom.:

132

Bravo

AF:

0.0476

Asia WGS

AF:

0.126

AC:

439

AN:

3478

EpiCase

AF:

0.0375

EpiControl

AF:

0.0324

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 31, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 20% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy, Progressive Myoclonus Epilepsy and Abnormal Movements and Neurodegeneration with brain iron accumulation. Number of patients: 19. Only high quality variants are reported. -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 06, 2013	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. -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2016

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

9.8

DANN

Benign

0.76

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