chr9-98303388-C-T
Variant names:
Variant summary
Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_005458.8(GABBR2):c.2265G>A(p.Thr755Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000384 in 1,614,140 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 0.000092 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000033 ( 0 hom. )
Consequence
GABBR2
NM_005458.8 synonymous
NM_005458.8 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.385
Publications
0 publications found
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]
GABBR2 Gene-Disease associations (from GenCC):
- developmental and epileptic encephalopathy, 59Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- neurodevelopmental disorder with poor language and loss of hand skillsInheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- atypical Rett syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Benign. The variant received -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
Variant 9-98303388-C-T is Benign according to our data. Variant chr9-98303388-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 462130.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.385 with no splicing effect.
BS2
High AC in GnomAd4 at 14 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GABBR2 | NM_005458.8 | c.2265G>A | p.Thr755Thr | synonymous_variant | Exon 16 of 19 | ENST00000259455.4 | NP_005449.5 | |
GABBR2 | XM_017015331.3 | c.1971G>A | p.Thr657Thr | synonymous_variant | Exon 15 of 18 | XP_016870820.1 | ||
GABBR2 | XM_005252316.6 | c.1491G>A | p.Thr497Thr | synonymous_variant | Exon 14 of 17 | XP_005252373.1 | ||
GABBR2 | XM_017015332.3 | c.1491G>A | p.Thr497Thr | synonymous_variant | Exon 13 of 16 | XP_016870821.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GABBR2 | ENST00000259455.4 | c.2265G>A | p.Thr755Thr | synonymous_variant | Exon 16 of 19 | 1 | NM_005458.8 | ENSP00000259455.2 | ||
GABBR2 | ENST00000634457.1 | c.492G>A | p.Thr164Thr | synonymous_variant | Exon 4 of 4 | 5 | ENSP00000489352.1 | |||
GABBR2 | ENST00000637410.1 | n.2043G>A | non_coding_transcript_exon_variant | Exon 16 of 19 | 5 | |||||
GABBR2 | ENST00000636575.1 | n.-54G>A | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152196Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
14
AN:
152196
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
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Gnomad ASJ
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Gnomad EAS
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Gnomad SAS
AF:
Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD2 exomes AF: 0.0000676 AC: 17AN: 251370 AF XY: 0.0000589 show subpopulations
GnomAD2 exomes
AF:
AC:
17
AN:
251370
AF XY:
Gnomad AFR exome
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Gnomad AMR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.0000328 AC: 48AN: 1461826Hom.: 0 Cov.: 32 AF XY: 0.0000358 AC XY: 26AN XY: 727222 show subpopulations
GnomAD4 exome
AF:
AC:
48
AN:
1461826
Hom.:
Cov.:
32
AF XY:
AC XY:
26
AN XY:
727222
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33480
American (AMR)
AF:
AC:
16
AN:
44722
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39698
South Asian (SAS)
AF:
AC:
0
AN:
86250
European-Finnish (FIN)
AF:
AC:
1
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
29
AN:
1111958
Other (OTH)
AF:
AC:
1
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.474
Heterozygous variant carriers
0
3
7
10
14
17
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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<30
30-35
35-40
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60-65
65-70
70-75
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>80
Age
GnomAD4 genome AF: 0.0000919 AC: 14AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74470 show subpopulations
GnomAD4 genome
AF:
AC:
14
AN:
152314
Hom.:
Cov.:
33
AF XY:
AC XY:
7
AN XY:
74470
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41570
American (AMR)
AF:
AC:
3
AN:
15306
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5172
South Asian (SAS)
AF:
AC:
0
AN:
4826
European-Finnish (FIN)
AF:
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
11
AN:
68024
Other (OTH)
AF:
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.493
Heterozygous variant carriers
0
1
2
4
5
6
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
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55-60
60-65
65-70
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>80
Age
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Epileptic encephalopathy Benign:1
Jul 24, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing
- -
not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:not provided
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
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
Publications
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