dbSNP rs9333567: ADRA2B:p.Thr12Thr (chr2-96116114-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000682.7(ADRA2B):c.36A>G(p.Thr12Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 1,611,556 control chromosomes in the GnomAD database, including 3,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.057 ( 369 hom., cov: 33)

Exomes 𝑓: 0.048 ( 2655 hom. )

Consequence

ADRA2B
NM_000682.7 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.14

Publications

16 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 -14 ACMG points.

BP4

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

BP6

Variant 2-96116114-T-C is Benign according to our data. Variant chr2-96116114-T-C is described in ClinVar as Benign. ClinVar VariationId is 3035382.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.14 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA2B	NM_000682.7 link	c.36A>G	p.Thr12Thr	synonymous_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.36A>G	p.Thr12Thr	synonymous_variant	Exon 1 of 1	6	NM_000682.7	ENSP00000480573.1		P18089

Frequencies

GnomAD3 genomes

AF:

0.0569

AC:

8655

AN:

152118

Hom.:

364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0677

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.0530

Gnomad EAS

AF:

0.179

Gnomad SAS

AF:

0.0478

Gnomad FIN

AF:

0.0270

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0363

Gnomad OTH

AF:

0.0589

GnomAD2 exomes

AF:

0.0693

AC:

16741

AN:

241692

AF XY:

0.0628

show subpopulations

Gnomad AFR exome

AF:

0.0661

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.0555

Gnomad EAS exome

AF:

0.181

Gnomad FIN exome

AF:

0.0283

Gnomad NFE exome

AF:

0.0386

Gnomad OTH exome

AF:

0.0662

GnomAD4 exome

AF:

0.0481

AC:

70141

AN:

1459320

Hom.:

2655

Cov.:

AF XY:

0.0470

AC XY:

34139

AN XY:

725860

show subpopulations

African (AFR)

AF:

0.0667

AC:

2231

AN:

33450

American (AMR)

AF:

0.163

AC:

7209

AN:

44356

Ashkenazi Jewish (ASJ)

AF:

0.0553

AC:

1439

AN:

26040

East Asian (EAS)

AF:

0.173

AC:

6870

AN:

39652

South Asian (SAS)

AF:

0.0368

AC:

3160

AN:

85796

European-Finnish (FIN)

AF:

0.0274

AC:

1444

AN:

52754

Middle Eastern (MID)

AF:

0.0427

AC:

246

AN:

5764

European-Non Finnish (NFE)

AF:

0.0394

AC:

43834

AN:

1111262

Other (OTH)

AF:

0.0615

AC:

3708

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

4095

8190

12284

16379

20474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1838

3676

5514

7352

9190

<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:

0.0570

AC:

8683

AN:

152236

Hom.:

369

Cov.:

AF XY:

0.0568

AC XY:

4224

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.0680

AC:

2828

AN:

41562

American (AMR)

AF:

0.104

AC:

1586

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0530

AC:

184

AN:

3472

East Asian (EAS)

AF:

0.179

AC:

923

AN:

5158

South Asian (SAS)

AF:

0.0479

AC:

231

AN:

4826

European-Finnish (FIN)

AF:

0.0270

AC:

287

AN:

10612

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0363

AC:

2467

AN:

67998

Other (OTH)

AF:

0.0597

AC:

126

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

434

869

1303

1738

2172

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0541

Hom.:

319

Bravo

AF:

0.0666

Asia WGS

AF:

0.117

AC:

407

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ADRA2B-related disorder

Benign:1

Apr 29, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.5

(source)

DANN

Benign

0.48

PhyloP100

-2.1

PromoterAI

0.016

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over