6-89265745-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002043.5(GABRR2):āc.757A>Gā(p.Ile253Val) variant causes a missense change. The variant allele was found at a frequency of 0.000158 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00014 ( 0 hom., cov: 32)
Exomes š: 0.00016 ( 0 hom. )
Consequence
GABRR2
NM_002043.5 missense
NM_002043.5 missense
Scores
1
7
9
Clinical Significance
Conservation
PhyloP100: 6.09
Genes affected
GABRR2 (HGNC:4091): (gamma-aminobutyric acid type A receptor subunit rho2) Gamma-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA receptors, which are ligand-gated chloride channels. The protein encoded by this gene is a member of the rho subunit family and is a component of the GABA type A receptor complex. This gene exists on chromosome 6q next to the gene encoding the rho 1 subunit of the GABA type A receptor, in a region thought to be associated with susceptibility for psychiatric disorders and epilepsy. Polymorphisms in this gene may also be associated with alcohol dependence, and general cognitive ability. [provided by RefSeq, Apr 2016]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABRR2 | NM_002043.5 | c.757A>G | p.Ile253Val | missense_variant | 7/9 | ENST00000402938.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABRR2 | ENST00000402938.4 | c.757A>G | p.Ile253Val | missense_variant | 7/9 | 1 | NM_002043.5 | P1 | |
GABRR2 | ENST00000602432.1 | n.588A>G | non_coding_transcript_exon_variant | 4/6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000145 AC: 22AN: 152096Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000131 AC: 33AN: 251434Hom.: 1 AF XY: 0.000118 AC XY: 16AN XY: 135890
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GnomAD4 exome AF: 0.000159 AC: 233AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.000194 AC XY: 141AN XY: 727232
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GnomAD4 genome AF: 0.000145 AC: 22AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74296
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 17, 2022 | The c.832A>G (p.I278V) alteration is located in exon 7 (coding exon 7) of the GABRR2 gene. This alteration results from a A to G substitution at nucleotide position 832, causing the isoleucine (I) at amino acid position 278 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D
M_CAP
Benign
D
MetaRNN
Uncertain
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Uncertain
T
REVEL
Uncertain
Sift4G
Uncertain
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at