rs780199000
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_198904.4(GABRG2):c.1088G>A(p.Arg363Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000254 in 1,613,916 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R363G) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
GABRG2
NM_198904.4 missense
NM_198904.4 missense
Scores
2
7
4
Clinical Significance
Conservation
PhyloP100: 6.85
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 Likely_benign. Variant got -3 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, GABRG2
BS2
?
High AC in GnomAdExome at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRG2 | NM_198904.4 | c.1088G>A | p.Arg363Gln | missense_variant | 8/10 | ENST00000639213.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRG2 | ENST00000639213.2 | c.1088G>A | p.Arg363Gln | missense_variant | 8/10 | 1 | NM_198904.4 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152040Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
4
AN:
152040
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251298Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135808
GnomAD3 exomes
AF:
AC:
5
AN:
251298
Hom.:
AF XY:
AC XY:
2
AN XY:
135808
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000253 AC: 37AN: 1461876Hom.: 0 Cov.: 32 AF XY: 0.0000261 AC XY: 19AN XY: 727238
GnomAD4 exome
AF:
AC:
37
AN:
1461876
Hom.:
Cov.:
32
AF XY:
AC XY:
19
AN XY:
727238
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152040Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74250
GnomAD4 genome
?
AF:
AC:
4
AN:
152040
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
74250
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
1
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 23, 2020 | This variant is associated with the following publications: (PMID: 21425109, 30660939) - |
Epilepsy, childhood absence 2;C1969810:Febrile seizures, familial, 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
Polyphen
0.30, 0.19
.;.;.;.;B;.;B;.;.;.;.;.;.;.
Vest4
0.79
MutPred
0.45
.;.;.;.;Loss of MoRF binding (P = 0.0635);.;Loss of MoRF binding (P = 0.0635);.;Loss of MoRF binding (P = 0.0635);.;Loss of MoRF binding (P = 0.0635);.;.;Loss of MoRF binding (P = 0.0635);
MVP
0.96
MPC
1.5
ClinPred
D
GERP RS
Varity_R
gMVP
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