dbSNP rs1554727793: GABBR2:p.Pro10Pro (chr9-98708708-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_005458.8(GABBR2):c.30C>T(p.Pro10Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000014 in 997,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P10P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000070 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

GABBR2
NM_005458.8 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.05

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 9-98708708-G-A is Benign according to our data. Variant chr9-98708708-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 462137.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.05 with no splicing effect.

BS2

High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GABBR2	NM_005458.8 link	c.30C>T	p.Pro10Pro	synonymous_variant	Exon 1 of 19	ENST00000259455.4	NP_005449.5	O75899H9NIL8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GABBR2	ENST00000259455.4 link	c.30C>T	p.Pro10Pro	synonymous_variant	Exon 1 of 19	1	NM_005458.8	ENSP00000259455.2		O75899

Frequencies

GnomAD3 genomes

AF:

0.00000705

AC:

AN:

141932

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000155

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000152

AC:

AN:

855796

Hom.:

Cov.:

AF XY:

0.0000200

AC XY:

AN XY:

399346

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16130

American (AMR)

AF:

0.00

AC:

AN:

1832

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5654

East Asian (EAS)

AF:

0.00

AC:

AN:

4466

South Asian (SAS)

AF:

0.00

AC:

AN:

17460

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2678

Middle Eastern (MID)

AF:

0.000579

AC:

AN:

1726

European-Non Finnish (NFE)

AF:

0.0000129

AC:

AN:

777290

Other (OTH)

AF:

0.0000700

AC:

AN:

28560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.540

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:

0.00000705

AC:

AN:

141932

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69014

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39226

American (AMR)

AF:

0.00

AC:

AN:

14458

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3334

East Asian (EAS)

AF:

0.00

AC:

AN:

4846

South Asian (SAS)

AF:

0.00

AC:

AN:

4600

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8038

Middle Eastern (MID)

AF:

0.00

AC:

AN:

276

European-Non Finnish (NFE)

AF:

0.0000155

AC:

AN:

64320

Other (OTH)

AF:

0.00

AC:

AN:

1956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epileptic encephalopathy

Benign:1

Nov 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.58

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

1.1

PromoterAI

0.054

Neutral

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over