rs397514556
Variant summary
Our verdict is Pathogenic. Variant got 19 ACMG points: 19P and 0B. PM1PM2PM5PP2PP3_StrongPP5_Very_Strong
The NM_000834.5(GRIN2B):c.1658C>T(p.Pro553Leu) 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. P553T) has been classified as 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.1658C>T | p.Pro553Leu | missense_variant | 9/14 | ENST00000609686.4 | |
LOC105369668 | XR_001749013.2 | n.484+1247G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIN2B | ENST00000609686.4 | c.1658C>T | p.Pro553Leu | missense_variant | 9/14 | 1 | NM_000834.5 | P1 | |
ENST00000652867.1 | n.203-3251G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 6 Pathogenic:2
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). - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Apr 07, 2022 | - - |
Developmental and epileptic encephalopathy, 27 Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Genetics and Molecular Pathology, SA Pathology | Aug 03, 2020 | The GRIN2B c.1658C>T missense variant is classified as LIKELY PATHOGENIC (PM2, PP3, PP5, PS2) The GRIN2B c.1658C>T missense variant is a single nucleotide change in exon 8 of the GRIN2B gene, which is predicted to change the amino acid proline at position 553 in the protein to leucine. This variant has been reported in a patient with severe intellectual disability and hypotonia, with early post-natal onset (PMID:23033978). In that patient, this variant was found to be de novo and was reported as likely pathogenic (PS2). This variant is in dbSNP (rs397514556) but is absent from population databases (PM2). This variant has been reported in ClinVar as Likely pathogenic by another diagnostic laboratory (Variation ID: VCV000039661.2), and has also been reported as damaging in HGMD (CM1211463) and pathogenic in LOVD (GRIN2B_000083) (PP5). Computational predictions support a deleterious effect on the gene or gene product (PP3). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at