rs200255226
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_000834.5(GRIN2B):c.3964G>C(p.Val1322Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another nucleotide change resulting in same amino acid change has been previously reported as Benignin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1322I) has been classified as Likely benign.
Frequency
Consequence
NM_000834.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRIN2B | NM_000834.5 | c.3964G>C | p.Val1322Leu | missense_variant | 14/14 | ENST00000609686.4 | |
GRIN2B | NM_001413992.1 | c.3964G>C | p.Val1322Leu | missense_variant | 15/15 | ||
GRIN2B | XM_005253351.3 | c.1750G>C | p.Val584Leu | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRIN2B | ENST00000609686.4 | c.3964G>C | p.Val1322Leu | missense_variant | 14/14 | 1 | NM_000834.5 | P1 | |
GRIN2B | ENST00000637214.1 | c.69+45329G>C | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251374Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135872
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461894Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727248
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Intellectual disability, autosomal dominant 6;C4015316:Developmental and epileptic encephalopathy, 27 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 10, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with GRIN2B-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces valine with leucine at codon 1322 of the GRIN2B protein (p.Val1322Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at