chr16-9829529-C-T
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001134407.3(GRIN2A):c.1901G>A(p.Trp634*) variant causes a stop gained 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 Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_001134407.3 stop_gained
Scores
Clinical Significance
Conservation
Publications
- complex neurodevelopmental disorderInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- Landau-Kleffner syndromeInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
- continuous spikes and waves during sleepInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutationInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- rolandic epilepsy-speech dyspraxia syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- self-limited epilepsy with centrotemporal spikesInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- neurodevelopmental disorderInheritance: AR Classification: LIMITED Submitted by: G2P
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ACMG classification
Our verdict: Pathogenic. The variant received 12 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Landau-Kleffner syndrome Pathogenic:1
For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 532718). This variant has not been reported in the literature in individuals affected with GRIN2A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp634*) in the GRIN2A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GRIN2A are known to be pathogenic (PMID: 23933819, 23933820). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at