rs1057524089
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_001134407.3(GRIN2A):c.487C>T(p.Gln163*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000684 in 1,460,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001134407.3 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1460934Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726796
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Landau-Kleffner syndrome Pathogenic:2
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This sequence change creates a premature translational stop signal (p.Gln163*) in the GRIN2A gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with GRIN2A-related disease. ClinVar contains an entry for this variant (Variation ID: 391457). Loss-of-function variants in GRIN2A are known to be pathogenic (PMID: 23933819, 23933820). For these reasons, this variant has been classified as Pathogenic. -
not provided Pathogenic:1
The Q163X nonsense variant in the GRIN2A gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q163X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although this pathogenic variant has not been reported previously to our knowledge, its presence is consistent with a diagnosis of GRIN2A-related disorder -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at