rs879253945
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1PM2PM5PP2PP3_ModeratePP5
The NM_000834.5(GRIN2B):c.1946A>G(p.Asn649Ser) 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N649T) 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 10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIN2B | NM_000834.5 | c.1946A>G | p.Asn649Ser | missense_variant | 10/14 | ENST00000609686.4 | |
LOC105369668 | XR_001749013.2 | n.252T>C | non_coding_transcript_exon_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIN2B | ENST00000609686.4 | c.1946A>G | p.Asn649Ser | missense_variant | 10/14 | 1 | NM_000834.5 | P1 | |
ENST00000652867.1 | n.203-6431T>C | intron_variant, non_coding_transcript_variant | |||||||
GRIN2B | ENST00000637214.1 | c.5A>G | p.Asn2Ser | missense_variant | 1/2 | 5 | |||
GRIN2B | ENST00000628166.2 | n.206A>G | non_coding_transcript_exon_variant | 2/5 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Dec 06, 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; Has not been previously published as pathogenic or benign to our knowledge - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jan 11, 2016 | - - |
Developmental and epileptic encephalopathy, 27 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | 3billion | Jan 03, 2022 | The is not observed in the gnomAD v2.1.1 dataset (PM2_M). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.623, 3CNET: 0.996, PP3_P). A missense variant is a common mechanism associated with Developmental and epileptic encephalopathy 27 (PP2_P). Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at