12-13564162-C-T
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 1P and 11B. PP2BP4_ModerateBP6BS1BS2
The NM_000834.5(GRIN2B):c.3076G>A(p.Gly1026Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000263 in 1,614,052 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
Consequence
NM_000834.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GRIN2B | NM_000834.5 | c.3076G>A | p.Gly1026Ser | missense_variant | Exon 14 of 14 | ENST00000609686.4 | NP_000825.2 | |
GRIN2B | NM_001413992.1 | c.3076G>A | p.Gly1026Ser | missense_variant | Exon 15 of 15 | NP_001400921.1 | ||
GRIN2B | XM_005253351.3 | c.862G>A | p.Gly288Ser | 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.3076G>A | p.Gly1026Ser | missense_variant | Exon 14 of 14 | 1 | NM_000834.5 | ENSP00000477455.1 | ||
GRIN2B | ENST00000637214.1 | c.69+44441G>A | intron_variant | Intron 1 of 1 | 5 | ENSP00000489997.1 |
Frequencies
GnomAD3 genomes AF: 0.000132 AC: 20AN: 152050Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000227 AC: 57AN: 251428Hom.: 0 AF XY: 0.000287 AC XY: 39AN XY: 135888
GnomAD4 exome AF: 0.000277 AC: 405AN: 1461884Hom.: 0 Cov.: 37 AF XY: 0.000311 AC XY: 226AN XY: 727242
GnomAD4 genome AF: 0.000131 AC: 20AN: 152168Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74366
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
This variant is associated with the following publications: (PMID: 27818011, 22986046, 22833210) -
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not specified Benign:1
Variant summary: GRIN2B c.3076G>A (p.Gly1026Ser) results in a non-conservative amino acid change located in the N-methyl D-aspartate receptor 2B3 C-terminus domain (IPR018884) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00023 in 251428 control chromosomes. c.3076G>A has been reported in the literature in at least one individual affected with autism spectrum disorder, without evidence for causation (e.g. Tarabeux_2011). This report does not provide unequivocal conclusions about association of the variant with Mental Retardation, Autosomal Dominant 6. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 22833210). ClinVar contains an entry for this variant (Variation ID: 205716). Based on the evidence outlined above, the variant was classified as likely benign. -
Inborn genetic diseases Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
GRIN2B-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Intellectual disability, autosomal dominant 6;C4015316:Developmental and epileptic encephalopathy, 27 Benign:1
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Developmental and epileptic encephalopathy, 27 Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at