rs771637982
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PM4_SupportingBS2
The NM_005458.8(GABBR2):c.2774_2776dupCCC(p.Pro925dup) variant causes a conservative inframe insertion change. The variant allele was found at a frequency of 0.00000902 in 1,441,334 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000066 ( 1 hom., cov: 31)
Exomes 𝑓: 0.0000023 ( 0 hom. )
Consequence
GABBR2
NM_005458.8 conservative_inframe_insertion
NM_005458.8 conservative_inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.53
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, Labcorp Genetics (formerly Invitae), Ambry Genetics
- neurodevelopmental disorder with poor language and loss of hand skillsInheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- complex neurodevelopmental disorderInheritance: AD Classification: MODERATE Submitted by: ClinGen
- atypical Rett syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
new If you want to explore the variant's impact on the transcript NM_005458.8, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.
ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_005458.8. Strenght limited to Supporting due to length of the change: 1aa.
BS2
High AC in GnomAd4 at 10 AD gene.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_005458.8. You can select a different transcript below to see updated ACMG assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| GABBR2 | TSL:1 MANE Select | c.2774_2776dupCCC | p.Pro925dup | conservative_inframe_insertion | Exon 19 of 19 | ENSP00000259455.2 | O75899 | ||
| GABBR2 | c.2708_2710dupCCC | p.Pro903dup | conservative_inframe_insertion | Exon 18 of 18 | ENSP00000601585.1 | ||||
| GABBR2 | c.2693_2695dupCCC | p.Pro898dup | conservative_inframe_insertion | Exon 18 of 18 | ENSP00000617435.1 |
Frequencies
GnomAD3 genomes 0.0000658 AC: 10AN: 152008Hom.: 1 Cov.: 31 show subpopulations
GnomAD3 genomes
AF:
AC:
10
AN:
152008
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000233 AC: 3AN: 1289326Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 631306 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1289326
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
631306
show subpopulations
African (AFR)
AF:
AC:
0
AN:
25762
American (AMR)
AF:
AC:
0
AN:
17100
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19944
East Asian (EAS)
AF:
AC:
0
AN:
30968
South Asian (SAS)
AF:
AC:
0
AN:
56458
European-Finnish (FIN)
AF:
AC:
0
AN:
49030
Middle Eastern (MID)
AF:
AC:
0
AN:
4960
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1032288
Other (OTH)
AF:
AC:
3
AN:
52816
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000658 AC: 10AN: 152008Hom.: 1 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74232 show subpopulations
GnomAD4 genome
AF:
AC:
10
AN:
152008
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
74232
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41400
American (AMR)
AF:
AC:
10
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3464
East Asian (EAS)
AF:
AC:
0
AN:
5172
South Asian (SAS)
AF:
AC:
0
AN:
4824
European-Finnish (FIN)
AF:
AC:
0
AN:
10572
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68004
Other (OTH)
AF:
AC:
0
AN:
2084
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.463
Heterozygous variant carriers
0
1
2
2
3
4
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Epileptic encephalopathy (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.
Publications
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