rs956362869
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4BP6
The NM_000834.5(GRIN2B):c.3028C>T(p.Pro1010Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000197 in 152,192 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 0.000020 ( 0 hom., cov: 33)
Consequence
GRIN2B
NM_000834.5 missense
NM_000834.5 missense
Scores
3
4
9
Clinical Significance
Conservation
PhyloP100: 7.12
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 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), GRIN2B. . Gene score misZ 5.4168 (greater than the threshold 3.09). Trascript score misZ 7.3273 (greater than threshold 3.09). GenCC has associacion of gene with 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=0.34823644).
BP6
Variant 12-13564210-G-A is Benign according to our data. Variant chr12-13564210-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 572441.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GRIN2B | NM_000834.5 | c.3028C>T | p.Pro1010Ser | missense_variant | 14/14 | ENST00000609686.4 | NP_000825.2 | |
GRIN2B | NM_001413992.1 | c.3028C>T | p.Pro1010Ser | missense_variant | 15/15 | NP_001400921.1 | ||
GRIN2B | XM_005253351.3 | c.814C>T | p.Pro272Ser | missense_variant | 4/4 | XP_005253408.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GRIN2B | ENST00000609686.4 | c.3028C>T | p.Pro1010Ser | missense_variant | 14/14 | 1 | NM_000834.5 | ENSP00000477455.1 | ||
GRIN2B | ENST00000637214.1 | c.69+44393C>T | intron_variant | 5 | ENSP00000489997.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 33
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GnomAD4 exome Cov.: 37
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152192Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74348
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 27 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Génétique des Maladies du Développement, Hospices Civils de Lyon | Aug 11, 2017 | - - |
Intellectual disability, autosomal dominant 6;C4015316:Developmental and epileptic encephalopathy, 27 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 03, 2023 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
D
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
PrimateAI
Benign
T
Sift4G
Benign
T
Polyphen
B
Vest4
MutPred
Loss of loop (P = 0.0112);
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