rs779830552

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_ModerateBP6_ModerateBS2

The NM_000834.5(GRIN2B):​c.4229C>T​(p.Thr1410Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000103 in 1,461,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

GRIN2B
NM_000834.5 missense

Scores

1
3
12

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.19
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

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=0.20476821).
BP6
Variant 12-13563009-G-A is Benign according to our data. Variant chr12-13563009-G-A is described in ClinVar as [Benign]. Clinvar id is 577792.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAdExome4 at 15 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GRIN2BNM_000834.5 linkc.4229C>T p.Thr1410Met missense_variant Exon 14 of 14 ENST00000609686.4 NP_000825.2 Q13224A0A8D9PHB2
GRIN2BNM_001413992.1 linkc.4229C>T p.Thr1410Met missense_variant Exon 15 of 15 NP_001400921.1
GRIN2BXM_005253351.3 linkc.2015C>T p.Thr672Met 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.4229C>T p.Thr1410Met missense_variant Exon 14 of 14 1 NM_000834.5 ENSP00000477455.1 Q13224
GRIN2BENST00000637214.1 linkc.69+45594C>T intron_variant Intron 1 of 1 5 ENSP00000489997.1 A0A1B0GU78

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251242
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000109
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000103
AC:
15
AN:
1461466
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
726962
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000504
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000720
Gnomad4 OTH exome
AF:
0.0000331
GnomAD4 genome
Cov.:
33
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Intellectual disability, autosomal dominant 6;C4015316:Developmental and epileptic encephalopathy, 27 Benign:1
Feb 29, 2024
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
AlphaMissense
Benign
0.080
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.40
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.38
T
Eigen
Uncertain
0.20
Eigen_PC
Uncertain
0.34
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.0015
T
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.45
T
Sift4G
Benign
0.062
T
Polyphen
0.79
P
Vest4
0.22
MutPred
0.38
Loss of phosphorylation at T1410 (P = 0.0474);
MVP
0.41
MPC
0.74
ClinPred
0.53
D
GERP RS
5.2
Varity_R
0.066
gMVP
0.37

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: rs779830552; hg19: chr12-13715943; API