rs211035
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_198903.2(GABRG2):āc.643A>Cā(p.Ile215Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 31)
Exomes š: 0.0000033 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GABRG2
NM_198903.2 missense
NM_198903.2 missense
Scores
16
Clinical Significance
Conservation
PhyloP100: -1.00
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant in the GABRG2 gene, where missense mutations are typically associated with disease (based on misZ statistic). The gene has 34 curated pathogenic missense variants (we use a threshold of 10). The gene has 21 curated benign missense variants. Gene score misZ: 2.9939 (below the threshold of 3.09). Trascript score misZ: 3.9088 (above the threshold of 3.09). GenCC associations: The gene is linked to epilepsy, Dravet syndrome, undetermined early-onset epileptic encephalopathy, generalized epilepsy with febrile seizures plus, developmental and epileptic encephalopathy, 74, febrile seizures, familial, 8, childhood epilepsy with centrotemporal spikes.
BP4
Computational evidence support a benign effect (MetaRNN=0.06712797).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000331 AC: 1AN: 302036Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 172116
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
AC:
1
AN:
302036
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
172116
Gnomad4 AFR exome
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GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | GABRG2: PM2, PP2, BP4 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;.
Vest4
MutPred
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
Name
Calibrated prediction
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Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at