Genetic Variant ADRA2B:c.*850T>G (chr2-96113947-A-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.*850T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0144 in 985,830 control chromosomes in the GnomAD database, including 448 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 0.029 ( 310 hom., cov: 33)

Exomes 𝑓: 0.012 ( 138 hom. )

Consequence

ADRA2B
NM_000682.7 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.355

Publications

6 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=-0.85).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA2B	NM_000682.7 link	c.*850T>G		3_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.*850T>G		3_prime_UTR_variant	Exon 1 of 1	6	NM_000682.7	ENSP00000480573.1		P18089

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4452

AN:

152184

Hom.:

307

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00514

Gnomad AMI

AF:

0.0363

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.0193

Gnomad EAS

AF:

0.137

Gnomad SAS

AF:

0.0602

Gnomad FIN

AF:

0.00894

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0112

Gnomad OTH

AF:

0.0401

GnomAD4 exome

AF:

0.0117

AC:

9722

AN:

833526

Hom.:

138

Cov.:

AF XY:

0.0118

AC XY:

4539

AN XY:

384970

show subpopulations

African (AFR)

AF:

0.00469

AC:

AN:

15786

American (AMR)

AF:

0.216

AC:

213

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.0235

AC:

121

AN:

5152

East Asian (EAS)

AF:

0.144

AC:

522

AN:

3628

South Asian (SAS)

AF:

0.0537

AC:

884

AN:

16458

European-Finnish (FIN)

AF:

0.0101

AC:

AN:

696

Middle Eastern (MID)

AF:

0.0327

AC:

AN:

1620

European-Non Finnish (NFE)

AF:

0.00955

AC:

7275

AN:

761900

Other (OTH)

AF:

0.0210

AC:

573

AN:

27302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

490

981

1471

1962

2452

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

436

872

1308

1744

2180

<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:

0.0293

AC:

4468

AN:

152304

Hom.:

310

Cov.:

AF XY:

0.0316

AC XY:

2350

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00512

AC:

213

AN:

41574

American (AMR)

AF:

0.144

AC:

2199

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0193

AC:

AN:

3472

East Asian (EAS)

AF:

0.137

AC:

711

AN:

5180

South Asian (SAS)

AF:

0.0611

AC:

295

AN:

4828

European-Finnish (FIN)

AF:

0.00894

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0112

AC:

763

AN:

68016

Other (OTH)

AF:

0.0402

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

196

393

589

786

982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0246

Hom.:

330

Bravo

AF:

0.0457

Asia WGS

AF:

0.0810

AC:

280

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.1

(source)

DANN

Benign

0.67

PhyloP100

-0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over