chr5-162068002-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1
The NM_198904.4(GABRG2):c.3G>T(p.Met1?) variant causes a start lost change. The variant allele was found at a frequency of 0.00000484 in 1,446,222 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
GABRG2
NM_198904.4 start_lost
NM_198904.4 start_lost
Scores
4
3
4
Clinical Significance
Conservation
PhyloP100: 4.32
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_pathogenic. Variant got 8 ACMG points.
PVS1
?
Start lost variant, no new inframe start found.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRG2 | NM_198904.4 | c.3G>T | p.Met1? | start_lost | 1/10 | ENST00000639213.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRG2 | ENST00000639213.2 | c.3G>T | p.Met1? | start_lost | 1/10 | 1 | NM_198904.4 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
GnomAD4 exome AF: 0.00000484 AC: 7AN: 1446222Hom.: 0 Cov.: 32 AF XY: 0.00000556 AC XY: 4AN XY: 719768
GnomAD4 exome
AF:
AC:
7
AN:
1446222
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
719768
Gnomad4 AFR exome
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GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Epilepsy, childhood absence 2;C1969810:Febrile seizures, familial, 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 02, 2023 | This sequence change affects the initiator methionine of the GABRG2 mRNA. The next in-frame methionine is located at codon 23. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GABRG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1479603). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
Polyphen
B;B;.;.;.;.;.
Vest4
0.81, 0.83
MutPred
Gain of catalytic residue at M1 (P = 0.0496);Gain of catalytic residue at M1 (P = 0.0496);Gain of catalytic residue at M1 (P = 0.0496);Gain of catalytic residue at M1 (P = 0.0496);Gain of catalytic residue at M1 (P = 0.0496);Gain of catalytic residue at M1 (P = 0.0496);Gain of catalytic residue at M1 (P = 0.0496);
MVP
0.98
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