chr9-98489394-T-C

Variant names:

• chr9-98489394-T-C
• rs2779550
• NM_005458.8:c.732+7019A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005458.8(GABBR2):​c.732+7019A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.967 in 152,300 control chromosomes in the GnomAD database, including 71,273 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.97 (71273 hom., cov: 32)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.683
• Publications: 2 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)
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: ClinGen
• atypical Rett syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.984 is higher than 0.05.

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.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR2	NM_005458.8	MANE Select	c.732+7019A>G		intron	N/A	NP_005449.5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GABBR2	ENST00000259455.4	TSL:1 MANE Select	c.732+7019A>G		intron	N/A	ENSP00000259455.2	O75899
	GABBR2	ENST00000931526.1		c.732+7019A>G		intron	N/A	ENSP00000601585.1
	GABBR2	ENST00000947376.1		c.732+7019A>G		intron	N/A	ENSP00000617435.1

Frequencies

GnomAD3 genomes AF: 0.967 AC: 147194 AN: 152182 Hom.: 71216 Cov.: 32

Gnomad AFR AF: 0.992

Gnomad AMI AF: 0.986

Gnomad AMR AF: 0.951

Gnomad ASJ AF: 0.991

Gnomad EAS AF: 0.912

Gnomad SAS AF: 0.959

Gnomad FIN AF: 0.969

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.959

Gnomad OTH AF: 0.964

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

GnomAD4 genome AF: 0.967 AC: 147308 AN: 152300 Hom.: 71273 Cov.: 32 AF XY: 0.967 AC XY: 71979 AN XY: 74460

African (AFR) AF: 0.992 AC: 41237 AN: 41580

American (AMR) AF: 0.950 AC: 14540 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.991 AC: 3440 AN: 3472

East Asian (EAS) AF: 0.912 AC: 4704 AN: 5156

South Asian (SAS) AF: 0.960 AC: 4632 AN: 4826

European-Finnish (FIN) AF: 0.969 AC: 10283 AN: 10610

Middle Eastern (MID) AF: 0.983 AC: 289 AN: 294

European-Non Finnish (NFE) AF: 0.959 AC: 65252 AN: 68034

Other (OTH) AF: 0.961 AC: 2034 AN: 2116

Alfa AF: 0.974 Hom.: 18680

Bravo AF: 0.969

Asia WGS AF: 0.941 AC: 3271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.41
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2779550; hg19: chr9-101251676;