rs201963596

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_000834.5(GRIN2B):​c.3076G>C​(p.Gly1026Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

GRIN2B
NM_000834.5 missense

Scores

3
7
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.23
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the GRIN2B gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 135 curated pathogenic missense variants (we use a threshold of 10). The gene has 118 curated benign missense variants. Gene score misZ: 5.4168 (above the threshold of 3.09). Trascript score misZ: 7.3273 (above the threshold of 3.09). GenCC associations: The gene is linked to autism susceptibility 1, developmental and epileptic encephalopathy, 27, autosomal dominant non-syndromic intellectual disability, complex neurodevelopmental disorder, West syndrome, intellectual disability, autosomal dominant 6.
BP4
Computational evidence support a benign effect (MetaRNN=0.35958824).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRIN2BNM_000834.5 linkc.3076G>C p.Gly1026Arg missense_variant Exon 14 of 14 ENST00000609686.4 NP_000825.2 Q13224A0A8D9PHB2
GRIN2BNM_001413992.1 linkc.3076G>C p.Gly1026Arg missense_variant Exon 15 of 15 NP_001400921.1
GRIN2BXM_005253351.3 linkc.862G>C p.Gly288Arg missense_variant Exon 4 of 4 XP_005253408.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GRIN2BENST00000609686.4 linkc.3076G>C p.Gly1026Arg missense_variant Exon 14 of 14 1 NM_000834.5 ENSP00000477455.1 Q13224
GRIN2BENST00000637214.1 linkc.69+44441G>C intron_variant Intron 1 of 1 5 ENSP00000489997.1 A0A1B0GU78

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
37
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.68
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.29
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.51
D
Eigen
Uncertain
0.47
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.36
T
MetaSVM
Benign
-1.2
T
MutationAssessor
Benign
1.4
L
PrimateAI
Uncertain
0.66
T
Sift4G
Benign
0.18
T
Polyphen
0.80
P
Vest4
0.14
MutPred
0.39
Gain of sheet (P = 0.0036);
MVP
0.96
MPC
2.6
ClinPred
0.97
D
GERP RS
5.5
Varity_R
0.44
gMVP
0.73

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.

Other links and lift over

dbSNP: rs201963596; hg19: chr12-13717096; API