9-98290624-T-C
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_005458.8(GABBR2):c.2786A>G(p.His929Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000353 in 1,443,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000035 ( 0 hom. )
Consequence
GABBR2
NM_005458.8 missense
NM_005458.8 missense
Scores
3
5
11
Clinical Significance
Conservation
PhyloP100: 6.21
Genes affected
GABBR2 (HGNC:4507): (gamma-aminobutyric acid type B receptor subunit 2) The multi-pass membrane protein encoded by this gene belongs to the G-protein coupled receptor 3 family and GABA-B receptor subfamily. The GABA-B receptors inhibit neuronal activity through G protein-coupled second-messenger systems, which regulate the release of neurotransmitters, and the activity of ion channels and adenylyl cyclase. This receptor subunit forms an active heterodimeric complex with GABA-B receptor subunit 1, neither of which is effective on its own. Allelic variants of this gene have been associated with nicotine dependence.[provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, GABBR2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.062250823).
BP6
?
Variant 9-98290624-T-C is Benign according to our data. Variant chr9-98290624-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1247195.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GABBR2 | NM_005458.8 | c.2786A>G | p.His929Arg | missense_variant | 19/19 | ENST00000259455.4 | |
GABBR2 | XM_017015331.3 | c.2492A>G | p.His831Arg | missense_variant | 18/18 | ||
GABBR2 | XM_005252316.6 | c.2012A>G | p.His671Arg | missense_variant | 17/17 | ||
GABBR2 | XM_017015332.3 | c.2012A>G | p.His671Arg | missense_variant | 16/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GABBR2 | ENST00000259455.4 | c.2786A>G | p.His929Arg | missense_variant | 19/19 | 1 | NM_005458.8 | P1 | |
GABBR2 | ENST00000637410.1 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 152008Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000634 AC: 8AN: 126094Hom.: 0 AF XY: 0.0000428 AC XY: 3AN XY: 70030
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GnomAD4 exome AF: 0.0000348 AC: 45AN: 1291558Hom.: 0 Cov.: 31 AF XY: 0.0000411 AC XY: 26AN XY: 632538
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GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 152008Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3AN XY: 74262
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Epileptic encephalopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 16, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 20, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Pathogenic
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
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