Variant chr9-98290667-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The ENST00000259455.4(GABBR2):c.2743G>T(p.Val915Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000151 in 1,324,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

GABBR2
ENST00000259455.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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=0.1470288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GABBR2	NM_005458.8 linkuse as main transcript	c.2743G>T	p.Val915Phe	missense_variant	19/19	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3 linkuse as main transcript	c.2449G>T	p.Val817Phe	missense_variant	18/18		XP_016870820.1
GABBR2	XM_005252316.6 linkuse as main transcript	c.1969G>T	p.Val657Phe	missense_variant	17/17		XP_005252373.1
GABBR2	XM_017015332.3 linkuse as main transcript	c.1969G>T	p.Val657Phe	missense_variant	16/16		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4 linkuse as main transcript	c.2743G>T	p.Val915Phe	missense_variant	19/19	1	NM_005458.8	ENSP00000259455	P1
GABBR2	ENST00000637410.1 linkuse as main transcript	n.2521G>T		non_coding_transcript_exon_variant	19/19	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000151

AC:

AN:

1324086

Hom.:

Cov.:

AF XY:

0.00000306

AC XY:

AN XY:

653058

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 03, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.034

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Benign

-0.022

Eigen_PC

Benign

0.19

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.92

M_CAP

Benign

0.027

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.48

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.56

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.95

REVEL

Benign

0.23

Sift

Uncertain

0.010

Sift4G

Uncertain

0.021

Polyphen

0.072

Vest4

0.18

MutPred

0.14

Loss of sheet (P = 0.0457);

MVP

0.36

MPC

1.3

ClinPred

0.83

GERP RS

5.5

Varity_R

0.23

gMVP

0.36

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