rs750898498

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005458.8(GABBR2):c.2229+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000299 in 1,605,092 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

GABBR2
NM_005458.8 splice_region, intron

Scores

Splicing: ADA: 0.00009064

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.436

Publications

0 publications found

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 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

GABBR2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 9-98306113-G-A is Benign according to our data. Variant chr9-98306113-G-A is described in ClinVar as Benign. ClinVar VariationId is 462129.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
GABBR2	NM_005458.8 link	c.2229+8C>T	splice_region_variant, intron_variant	Intron 15 of 18	ENST00000259455.4	NP_005449.5
GABBR2	XM_017015331.3 link	c.1935+8C>T	splice_region_variant, intron_variant	Intron 14 of 17		XP_016870820.1
GABBR2	XM_005252316.6 link	c.1455+8C>T	splice_region_variant, intron_variant	Intron 13 of 16		XP_005252373.1
GABBR2	XM_017015332.3 link	c.1455+8C>T	splice_region_variant, intron_variant	Intron 12 of 15		XP_016870821.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4 link	c.2229+8C>T		splice_region_variant, intron_variant	Intron 15 of 18	1	NM_005458.8	ENSP00000259455.2

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000443

AC:

AN:

248054

AF XY:

0.0000522

show subpopulations

Gnomad AFR exome

AF:

0.000125

Gnomad AMR exome

AF:

0.0000581

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000275

AC:

AN:

1452774

Hom.:

Cov.:

AF XY:

0.0000304

AC XY:

AN XY:

723162

show subpopulations

African (AFR)

AF:

0.0000300

AC:

AN:

33318

American (AMR)

AF:

0.0000448

AC:

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26070

East Asian (EAS)

AF:

0.000278

AC:

AN:

39592

South Asian (SAS)

AF:

0.000221

AC:

AN:

85870

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00000362

AC:

AN:

1104218

Other (OTH)

AF:

0.0000499

AC:

AN:

60064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152318

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41572

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000622

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000378

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Aug 17, 2023

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.94

CADD

Benign

(source)

DANN

Benign

0.46

PhyloP100

-0.44

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000091

dbscSNV1_RF

Benign

0.022

SpliceAI score (max)

0.68

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.68

Position offset: 2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over