9-98481082-T-G

Variant names:

• chr9-98481082-T-G
• rs2808557
• NM_005458.8:c.733-85A>C

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.733-85A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.805 in 864,568 control chromosomes in the GnomAD database, including 282,626 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (43591 hom., cov: 32)
  • Exomes 𝑓: 0.82 (239035 hom.)
• Consequence: GABBR2 NM_005458.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0470
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-98481082-T-G is Benign according to our data. Variant chr9-98481082-T-G is described in ClinVar as Benign. ClinVar VariationId is 1223286.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.883 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.733-85A>C		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.733-85A>C		intron	N/A	ENSP00000259455.2	O75899
	GABBR2	ENST00000931526.1		c.733-7736A>C		intron	N/A	ENSP00000601585.1
	GABBR2	ENST00000947376.1		c.733-85A>C		intron	N/A	ENSP00000617435.1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113539 AN: 151994 Hom.: 43559 Cov.: 32

Gnomad AFR AF: 0.553

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.905

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.750

GnomAD4 exome AF: 0.817 AC: 582078 AN: 712456 Hom.: 239035 AF XY: 0.818 AC XY: 312756 AN XY: 382350

African (AFR) AF: 0.546 AC: 10485 AN: 19186

American (AMR) AF: 0.866 AC: 37550 AN: 43344

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 16927 AN: 20964

East Asian (EAS) AF: 0.909 AC: 32749 AN: 36046

South Asian (SAS) AF: 0.822 AC: 58110 AN: 70730

European-Finnish (FIN) AF: 0.824 AC: 42976 AN: 52176

Middle Eastern (MID) AF: 0.724 AC: 3104 AN: 4288

European-Non Finnish (NFE) AF: 0.818 AC: 351889 AN: 430198

Other (OTH) AF: 0.796 AC: 28288 AN: 35524

GnomAD4 genome AF: 0.747 AC: 113620 AN: 152112 Hom.: 43591 Cov.: 32 AF XY: 0.751 AC XY: 55850 AN XY: 74372

African (AFR) AF: 0.553 AC: 22928 AN: 41454

American (AMR) AF: 0.811 AC: 12402 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2796 AN: 3470

East Asian (EAS) AF: 0.905 AC: 4675 AN: 5166

South Asian (SAS) AF: 0.822 AC: 3971 AN: 4830

European-Finnish (FIN) AF: 0.824 AC: 8728 AN: 10592

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

European-Non Finnish (NFE) AF: 0.818 AC: 55619 AN: 67988

Other (OTH) AF: 0.747 AC: 1579 AN: 2114

Alfa AF: 0.783 Hom.: 18453

Bravo AF: 0.739

Asia WGS AF: 0.829 AC: 2880 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.4
DANN	Benign	0.55
PhyloP100		0.047
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: rs2808557; hg19: chr9-101243364;