rs2779547

Variant names:

• chr9-98480739-T-C
• rs2779547
• NM_005458.8:c.798+193A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005458.8(GABBR2):​c.798+193A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 151,892 control chromosomes in the GnomAD database, including 45,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.76 (45120 hom., cov: 30)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.43
• 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, 59

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• neurodevelopmental disorder with poor language and loss of hand skills

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• atypical Rett syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 9-98480739-T-C is Benign according to our data. Variant chr9-98480739-T-C is described in ClinVar as Benign. ClinVar VariationId is 1279836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.882 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.798+193A>G		intron_variant	Intron 5 of 18	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3	c.504+193A>G		intron_variant	Intron 4 of 17		XP_016870820.1
GABBR2	XM_005252316.6	c.24+193A>G		intron_variant	Intron 3 of 16		XP_005252373.1
GABBR2	XM_017015332.3	c.24+193A>G		intron_variant	Intron 2 of 15		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.798+193A>G		intron_variant	Intron 5 of 18	1	NM_005458.8	ENSP00000259455.2

Frequencies

GnomAD3 genomes AF: 0.765 AC: 116070 AN: 151774 Hom.: 45089 Cov.: 30

Gnomad AFR AF: 0.615

Gnomad AMI AF: 0.783

Gnomad AMR AF: 0.817

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.904

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.762

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.765 AC: 116152 AN: 151892 Hom.: 45120 Cov.: 30 AF XY: 0.768 AC XY: 57026 AN XY: 74214

African (AFR) AF: 0.615 AC: 25413 AN: 41332

American (AMR) AF: 0.817 AC: 12481 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2797 AN: 3470

East Asian (EAS) AF: 0.904 AC: 4651 AN: 5144

South Asian (SAS) AF: 0.823 AC: 3950 AN: 4802

European-Finnish (FIN) AF: 0.824 AC: 8708 AN: 10570

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.818 AC: 55628 AN: 67984

Other (OTH) AF: 0.759 AC: 1603 AN: 2112

Alfa AF: 0.787 Hom.: 6931

Bravo AF: 0.760

Asia WGS AF: 0.835 AC: 2901 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 15, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.63
DANN	Benign	0.34
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2779547; hg19: chr9-101243021;