rs779830552
Variant names:
Your query was ambiguous. Multiple possible variants found:
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
NM_000834.5 missense
Scores
1
3
12
Clinical Significance
Conservation
PhyloP100: 4.19
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 |
---|---|---|---|---|---|---|---|---|
GRIN2B | NM_000834.5 | c.4229C>T | p.Thr1410Met | missense_variant | Exon 14 of 14 | ENST00000609686.4 | NP_000825.2 | |
GRIN2B | NM_001413992.1 | c.4229C>T | p.Thr1410Met | missense_variant | Exon 15 of 15 | NP_001400921.1 | ||
GRIN2B | XM_005253351.3 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
GRIN2B | ENST00000609686.4 | c.4229C>T | p.Thr1410Met | missense_variant | Exon 14 of 14 | 1 | NM_000834.5 | ENSP00000477455.1 | ||
GRIN2B | ENST00000637214.1 | c.69+45594C>T | intron_variant | Intron 1 of 1 | 5 | ENSP00000489997.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251242Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135830
GnomAD3 exomes
AF:
AC:
2
AN:
251242
Hom.:
AF XY:
AC XY:
0
AN XY:
135830
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000103 AC: 15AN: 1461466Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 726962
GnomAD4 exome
AF:
AC:
15
AN:
1461466
Hom.:
Cov.:
31
AF XY:
AC XY:
8
AN XY:
726962
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
ExAC
AF:
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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
PrimateAI
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of phosphorylation at T1410 (P = 0.0474);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at