rs797044849
Variant summary
Our verdict is Pathogenic. Variant got 19 ACMG points: 19P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_000834.5(GRIN2B):c.2459G>T(p.Gly820Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G820A) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000834.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIN2B | NM_000834.5 | c.2459G>T | p.Gly820Val | missense_variant | 13/14 | ENST00000609686.4 | |
GRIN2B | NM_001413992.1 | c.2459G>T | p.Gly820Val | missense_variant | 14/15 | ||
GRIN2B | XM_005253351.3 | c.245G>T | p.Gly82Val | missense_variant | 3/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIN2B | ENST00000609686.4 | c.2459G>T | p.Gly820Val | missense_variant | 13/14 | 1 | NM_000834.5 | P1 | |
GRIN2B | ENST00000637214.1 | c.69+41439G>T | intron_variant | 5 | |||||
GRIN2B | ENST00000628166.2 | n.719G>T | non_coding_transcript_exon_variant | 5/5 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
GRIN2B-related disorder Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 30, 2023 | The GRIN2B c.2459G>T variant is predicted to result in the amino acid substitution p.Gly820Val. This missense change was documented de novo in at least two unrelated individuals with developmental delays and intellectual disability (Platzer et al. 2017. PubMed ID: 28377535, Ziats et al. 2020. PubMed ID: 31618753). Additionally, multiple patients with de novo variants leading to different amino acid substitutions at this residue have been reported with features consistent with GRIN2B-related disease (p.Gly820Arg, p.Gly820Ala, p.Gly820Glu; Platzer et al. 2017. PubMed ID: 28377535, Powis et al. 2020. PubMed ID: 31628766, Gao et al. 2018. PubMed ID: 30440138, Marinakis et al. 2021. PubMed ID: 34008892). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Feb 24, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27839871, 28377535, 27818011, 28636915, 31618753, 34568804) - |
Intellectual disability, autosomal dominant 6 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Apr 04, 2017 | This variant was identified as de novo (maternity and paternity confirmed). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at