Genetic Variant ADRA2B:c.-98C>G (chr2-96116247-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000682.7(ADRA2B):c.-98C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 1,150,960 control chromosomes in the GnomAD database, including 271,113 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 0.71 ( 39520 hom., cov: 33)

Exomes 𝑓: 0.68 ( 231593 hom. )

Consequence

ADRA2B
NM_000682.7 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.09

Publications

12 publications found

Variant links:

Genes affected

ADRA2B (HGNC:282): (adrenoceptor alpha 2B) This intronless gene encodes a seven-pass transmembrane protein. This protein is a member of a subfamily of G protein-coupled receptors that regulate neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. [provided by RefSeq, Apr 2014]

ADRA2B Gene-Disease associations (from GenCC):

benign adult familial myoclonic epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P
epilepsy, familial adult myoclonic, 2
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ADRA2B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.831 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA2B	NM_000682.7 link	c.-98C>G		5_prime_UTR_variant	Exon 1 of 1	ENST00000620793.2	NP_000673.2	P18089

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADRA2B	ENST00000620793.2 link	c.-98C>G		5_prime_UTR_variant	Exon 1 of 1	6	NM_000682.7	ENSP00000480573.1		P18089

Frequencies

GnomAD3 genomes

AF:

0.714

AC:

108488

AN:

151934

Hom.:

39495

Cov.:

show subpopulations

Gnomad AFR

AF:

0.839

Gnomad AMI

AF:

0.547

Gnomad AMR

AF:

0.705

Gnomad ASJ

AF:

0.801

Gnomad EAS

AF:

0.571

Gnomad SAS

AF:

0.781

Gnomad FIN

AF:

0.535

Gnomad MID

AF:

0.899

Gnomad NFE

AF:

0.670

Gnomad OTH

AF:

0.745

GnomAD4 exome

AF:

0.678

AC:

676871

AN:

998908

Hom.:

231593

Cov.:

AF XY:

0.682

AC XY:

344858

AN XY:

505316

show subpopulations

African (AFR)

AF:

0.852

AC:

19950

AN:

23414

American (AMR)

AF:

0.675

AC:

21220

AN:

31430

Ashkenazi Jewish (ASJ)

AF:

0.799

AC:

17518

AN:

21916

East Asian (EAS)

AF:

0.606

AC:

20421

AN:

33720

South Asian (SAS)

AF:

0.776

AC:

53887

AN:

69436

European-Finnish (FIN)

AF:

0.542

AC:

25053

AN:

46242

Middle Eastern (MID)

AF:

0.855

AC:

2829

AN:

3310

European-Non Finnish (NFE)

AF:

0.668

AC:

484648

AN:

725256

Other (OTH)

AF:

0.709

AC:

31345

AN:

44184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

11476

22951

34427

45902

57378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.714

AC:

108565

AN:

152052

Hom.:

39520

Cov.:

AF XY:

0.709

AC XY:

52727

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.838

AC:

34823

AN:

41534

American (AMR)

AF:

0.704

AC:

10771

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.801

AC:

2777

AN:

3468

East Asian (EAS)

AF:

0.571

AC:

2919

AN:

5110

South Asian (SAS)

AF:

0.780

AC:

3768

AN:

4830

European-Finnish (FIN)

AF:

0.535

AC:

5666

AN:

10584

Middle Eastern (MID)

AF:

0.895

AC:

263

AN:

294

European-Non Finnish (NFE)

AF:

0.670

AC:

45503

AN:

67918

Other (OTH)

AF:

0.747

AC:

1576

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1589

3178

4768

6357

7946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.689

Hom.:

4572

Bravo

AF:

0.726

Asia WGS

AF:

0.728

AC:

2528

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.13

(source)

DANN

Benign

0.41

PhyloP100

-1.1

PromoterAI

0.015

Neutral

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-96116247-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over