rs876661151
Variant summary
Our verdict is Pathogenic. Variant got 19 ACMG points: 19P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_000834.5(GRIN2B):c.2002G>T(p.Asp668Tyr) 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. D668N) 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.2002G>T | p.Asp668Tyr | missense_variant | 10/14 | ENST00000609686.4 | |
LOC105369668 | XR_001749013.2 | n.203-7C>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIN2B | ENST00000609686.4 | c.2002G>T | p.Asp668Tyr | missense_variant | 10/14 | 1 | NM_000834.5 | P1 | |
ENST00000652867.1 | n.203-6487C>A | intron_variant, non_coding_transcript_variant | |||||||
GRIN2B | ENST00000637214.1 | c.61G>T | p.Asp21Tyr | missense_variant | 1/2 | 5 | |||
GRIN2B | ENST00000628166.2 | n.262G>T | non_coding_transcript_exon_variant | 2/5 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 25, 2015 | The D668Y variant in the GRIN2B gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D668Y variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The D668Y variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. The D668Y variant is a strong candidate for a pathogenic variant. - |
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