chr9-98290634-G-A

Position:

chr9-98290634-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4BP6_ModerateBS2

The NM_005458.8(GABBR2):c.2776C>T(p.Arg926Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000152 in 1,447,252 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R926H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

GABBR2
NM_005458.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.53

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), GABBR2. . Gene score misZ 4.6253 (greater than the threshold 3.09). Trascript score misZ 4.0975 (greater than threshold 3.09). GenCC has associacion of gene with developmental and epileptic encephalopathy, 59, neurodevelopmental disorder with poor language and loss of hand skills, atypical Rett syndrome.

BP4

Computational evidence support a benign effect (MetaRNN=0.38686848).

BP6

Variant 9-98290634-G-A is Benign according to our data. Variant chr9-98290634-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 578900.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GABBR2	NM_005458.8 linkuse as main transcript	c.2776C>T	p.Arg926Cys	missense_variant	19/19	ENST00000259455.4
GABBR2	XM_017015331.3 linkuse as main transcript	c.2482C>T	p.Arg828Cys	missense_variant	18/18
GABBR2	XM_005252316.6 linkuse as main transcript	c.2002C>T	p.Arg668Cys	missense_variant	17/17
GABBR2	XM_017015332.3 linkuse as main transcript	c.2002C>T	p.Arg668Cys	missense_variant	16/16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GABBR2	ENST00000259455.4 linkuse as main transcript	c.2776C>T	p.Arg926Cys	missense_variant	19/19	1	NM_005458.8	P1
GABBR2	ENST00000637410.1 linkuse as main transcript			downstream_gene_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.0000337

AC:

AN:

118818

Hom.:

AF XY:

0.0000151

AC XY:

AN XY:

66178

show subpopulations

Gnomad AFR exome

AF:

0.000138

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000295

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000163

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000131

AC:

AN:

1294976

Hom.:

Cov.:

AF XY:

0.00000945

AC XY:

AN XY:

634672

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000692

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000106

Gnomad4 OTH exome

AF:

0.0000377

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.0000667

Hom.:

Bravo

AF:

0.0000378

ExAC

AF:

0.0000332

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.080

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.39

MetaSVM

Uncertain

0.26

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.80

REVEL

Uncertain

0.46

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.56

MVP

0.73

MPC

2.3

ClinPred

0.52

GERP RS

5.5

Varity_R

0.39

gMVP

0.43

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over