rs1060501889
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_198904.4(GABRG2):c.1025del(p.Cys342PhefsTer58) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
GABRG2
NM_198904.4 frameshift
NM_198904.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.88
Genes affected
GABRG2 (HGNC:4087): (gamma-aminobutyric acid type A receptor subunit gamma2) This gene encodes a gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the mammlian brain, where it acts at GABA-A receptors, which are ligand-gated chloride channels. GABA-A receptors are pentameric, consisting of proteins from several subunit classes: alpha, beta, gamma, delta and rho. Mutations in this gene have been associated with epilepsy and febrile seizures. Multiple transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 5-162149209-TG-T is Pathogenic according to our data. Variant chr5-162149209-TG-T is described in ClinVar as [Pathogenic]. Clinvar id is 408213.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRG2 | NM_198904.4 | c.1025del | p.Cys342PhefsTer58 | frameshift_variant | 8/10 | ENST00000639213.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRG2 | ENST00000639213.2 | c.1025del | p.Cys342PhefsTer58 | frameshift_variant | 8/10 | 1 | NM_198904.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Epilepsy, childhood absence 2;C1969810:Febrile seizures, familial, 8 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 06, 2019 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in GABRG2 are known to be pathogenic (PMID: 22539854, 22750526, 24407264). This variant has not been reported in the literature in individuals with GABRG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 408213). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Cys342Phefs*50) in the GABRG2 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at