Genetic Variant NM_000682.7:c.903_911delAGAGGAGGA (chr2-96115238-CTCCTCCTCT-C) – ACMG Classification: Benign (-17 pts)

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3BP6_Very_StrongBA1

The NM_000682.7(ADRA2B):c.903_911delAGAGGAGGA(p.Glu302_Glu304del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 1,557,570 control chromosomes in the GnomAD database, including 81,834 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6816 hom., cov: 20)

Exomes 𝑓: 0.32 ( 75018 hom. )

Consequence

ADRA2B
NM_000682.7 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.02

Publications

3 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 -17 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_000682.7

BP6

Variant 2-96115238-CTCCTCCTCT-C is Benign according to our data. Variant chr2-96115238-CTCCTCCTCT-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 767169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA2B	NM_000682.7 link	c.903_911delAGAGGAGGA	p.Glu302_Glu304del	disruptive_inframe_deletion	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.903_911delAGAGGAGGA	p.Glu302_Glu304del	disruptive_inframe_deletion	Exon 1 of 1	6	NM_000682.7	ENSP00000480573.1		P18089

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

43000

AN:

151702

Hom.:

6808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.157

Gnomad AMI

AF:

0.444

Gnomad AMR

AF:

0.293

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.423

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.462

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.329

Gnomad OTH

AF:

0.252

GnomAD4 exome

AF:

0.322

AC:

453186

AN:

1405750

Hom.:

75018

AF XY:

0.318

AC XY:

220878

AN XY:

694002

show subpopulations

African (AFR)

AF:

0.142

AC:

4542

AN:

31894

American (AMR)

AF:

0.327

AC:

11922

AN:

36418

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

4997

AN:

24970

East Asian (EAS)

AF:

0.394

AC:

14343

AN:

36402

South Asian (SAS)

AF:

0.223

AC:

17960

AN:

80508

European-Finnish (FIN)

AF:

0.456

AC:

22622

AN:

49580

Middle Eastern (MID)

AF:

0.146

AC:

830

AN:

5694

European-Non Finnish (NFE)

AF:

0.332

AC:

359155

AN:

1081936

Other (OTH)

AF:

0.288

AC:

16815

AN:

58348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

19121

38241

57362

76482

95603

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11794

23588

35382

47176

58970

<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:

0.283

AC:

43041

AN:

151820

Hom.:

6816

Cov.:

AF XY:

0.288

AC XY:

21392

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.158

AC:

6540

AN:

41500

American (AMR)

AF:

0.293

AC:

4474

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

693

AN:

3472

East Asian (EAS)

AF:

0.423

AC:

2163

AN:

5108

South Asian (SAS)

AF:

0.219

AC:

1054

AN:

4808

European-Finnish (FIN)

AF:

0.462

AC:

4877

AN:

10552

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.329

AC:

22281

AN:

67814

Other (OTH)

AF:

0.250

AC:

529

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

1438

2876

4313

5751

7189

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<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:

0.0144

Hom.:

2779

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Feb 16, 2025

Laboratory of Genetics, Children's Clinical University Hospital Latvia

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Dec 19, 2019

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

PhyloP100

2.0

Splicing

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