9-98515611-G-T

Variant names:

• chr9-98515611-G-T
• rs2808566
• NM_005458.8:c.631-19097C>A

Variant summary

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

The NM_005458.8(GABBR2):​c.631-19097C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,688 control chromosomes in the GnomAD database, including 18,491 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 0.49 (18491 hom., cov: 30)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.233
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.738 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8	c.631-19097C>A		intron_variant	Intron 3 of 18	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3	c.337-19097C>A		intron_variant	Intron 2 of 17		XP_016870820.1
GABBR2	XM_005252316.6	c.-144-19097C>A		intron_variant	Intron 1 of 16		XP_005252373.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4	c.631-19097C>A		intron_variant	Intron 3 of 18	1	NM_005458.8	ENSP00000259455.2

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73700 AN: 151570 Hom.: 18470 Cov.: 30

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.543

Gnomad EAS AF: 0.757

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.525

Gnomad MID AF: 0.414

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.486 AC: 73772 AN: 151688 Hom.: 18491 Cov.: 30 AF XY: 0.493 AC XY: 36546 AN XY: 74094

African (AFR) AF: 0.379 AC: 15691 AN: 41354

American (AMR) AF: 0.568 AC: 8660 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.543 AC: 1885 AN: 3472

East Asian (EAS) AF: 0.758 AC: 3878 AN: 5118

South Asian (SAS) AF: 0.552 AC: 2650 AN: 4798

European-Finnish (FIN) AF: 0.525 AC: 5522 AN: 10518

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.497 AC: 33735 AN: 67870

Other (OTH) AF: 0.513 AC: 1079 AN: 2104

Alfa AF: 0.335 Hom.: 897

Bravo AF: 0.488

Asia WGS AF: 0.637 AC: 2216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.1
DANN	Benign	0.77
PhyloP100		0.23
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: rs2808566; hg19: chr9-101277893;