5-162149295-TAAA-T
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Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 1P and 9B. PM4_SupportingBP6BS1BS2
The NM_198904.4(GABRG2):c.1113_1115del(p.Lys374del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,614,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000068 ( 0 hom. )
Consequence
GABRG2
NM_198904.4 inframe_deletion
NM_198904.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 8.84
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 Benign. Variant got -8 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_198904.4. Strenght limited to Supporting due to length of the change: 1aa.
BP6
Variant 5-162149295-TAAA-T is Benign according to our data. Variant chr5-162149295-TAAA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 167117.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=3, Likely_benign=2}.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0000329 (5/152152) while in subpopulation NFE AF= 0.0000735 (5/68028). AF 95% confidence interval is 0.0000285. There are 0 homozygotes in gnomad4. There are 1 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRG2 | NM_198904.4 | c.1113_1115del | p.Lys374del | inframe_deletion | 8/10 | ENST00000639213.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRG2 | ENST00000639213.2 | c.1113_1115del | p.Lys374del | inframe_deletion | 8/10 | 1 | NM_198904.4 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152152Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251258Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135786
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GnomAD4 exome AF: 0.0000677 AC: 99AN: 1461858Hom.: 0 AF XY: 0.0000715 AC XY: 52AN XY: 727228
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74328
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:3Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 03, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 30, 2019 | This variant is associated with the following publications: (PMID: 30660939) - |
Epilepsy, childhood absence 2;C1969810:Febrile seizures, familial, 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 2023 | This variant, c.1113_1115del, results in the deletion of 1 amino acid(s) of the GABRG2 protein (p.Lys374del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs749611954, gnomAD 0.01%). This variant has been observed in individual(s) with epilepsy (PMID: 30660939). ClinVar contains an entry for this variant (Variation ID: 167117). 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. - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at