12-13562800-TA-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PVS1_ModeratePM2
The NM_000834.5(GRIN2B):c.4437delT(p.Ser1479ArgfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000834.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GRIN2B | NM_000834.5 | c.4437delT | p.Ser1479ArgfsTer8 | frameshift_variant | Exon 14 of 14 | ENST00000609686.4 | NP_000825.2 | |
GRIN2B | NM_001413992.1 | c.4437delT | p.Ser1479ArgfsTer8 | frameshift_variant | Exon 15 of 15 | NP_001400921.1 | ||
GRIN2B | XM_005253351.3 | c.2223delT | p.Ser741ArgfsTer8 | frameshift_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.4437delT | p.Ser1479ArgfsTer8 | frameshift_variant | Exon 14 of 14 | 1 | NM_000834.5 | ENSP00000477455.1 | ||
GRIN2B | ENST00000637214.1 | c.69+45802delT | intron_variant | Intron 1 of 1 | 5 | ENSP00000489997.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 30
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 6;C4015316:Developmental and epileptic encephalopathy, 27 Uncertain:1
This sequence change results in a frameshift in the GRIN2B gene (p.Ser1479Argfs*8). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 6 amino acid(s) of the GRIN2B protein and extend the protein by 1 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GRIN2B-related conditions. ClinVar contains an entry for this variant (Variation ID: 856799). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at