rs374746622
Positions:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 1P and 10B. PP2BP4BP6BS1BS2
The NM_000834.5(GRIN2B):c.3922G>A(p.Val1308Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000458 in 1,614,074 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000048 ( 0 hom. )
Consequence
GRIN2B
NM_000834.5 missense
NM_000834.5 missense
Scores
1
5
10
Clinical Significance
Conservation
PhyloP100: 3.64
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 Benign. Variant got -9 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, GRIN2B
BP4
?
Computational evidence support a benign effect (MetaRNN=0.39057577).
BP6
?
Variant 12-13563316-C-T is Benign according to our data. Variant chr12-13563316-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 373230.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0000263 (4/152188) while in subpopulation AMR AF= 0.000131 (2/15286). AF 95% confidence interval is 0.0000226. There are 0 homozygotes in gnomad4. There are 2 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAdExome4 at 70 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIN2B | NM_000834.5 | c.3922G>A | p.Val1308Met | missense_variant | 14/14 | ENST00000609686.4 | |
GRIN2B | NM_001413992.1 | c.3922G>A | p.Val1308Met | missense_variant | 15/15 | ||
GRIN2B | XM_005253351.3 | c.1708G>A | p.Val570Met | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIN2B | ENST00000609686.4 | c.3922G>A | p.Val1308Met | missense_variant | 14/14 | 1 | NM_000834.5 | P1 | |
GRIN2B | ENST00000637214.1 | c.69+45287G>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152188Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251330Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135892
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GnomAD4 exome AF: 0.0000479 AC: 70AN: 1461886Hom.: 0 Cov.: 33 AF XY: 0.0000509 AC XY: 37AN XY: 727242
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74340
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 26, 2017 | The p.V1308M variant (also known as c.3922G>A), located in coding exon 12 of the GRIN2B gene, results from a G to A substitution at nucleotide position 3922. The valine at codon 1308 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Intellectual disability, autosomal dominant 6;C4015316:Developmental and epileptic encephalopathy, 27 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 26, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at