Genetic Variant ADRA2B:p.Glu302_Glu304dup (chr2-96115238-C-CTCCTCCTCT) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP3BP6_Moderate

The NM_000682.7(ADRA2B):c.903_911dupAGAGGAGGA(p.Glu302_Glu304dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,106 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

ADRA2B
NM_000682.7 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.54

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP3

Nonframeshift variant in repetitive region in NM_000682.7

BP6

Variant 2-96115238-C-CTCCTCCTCT is Benign according to our data. Variant chr2-96115238-C-CTCCTCCTCT is described in ClinVar as Benign. ClinVar VariationId is 3035246.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADRA2B	NM_000682.7 link	c.903_911dupAGAGGAGGA	p.Glu302_Glu304dup	disruptive_inframe_insertion	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_911dupAGAGGAGGA	p.Glu302_Glu304dup	disruptive_inframe_insertion	Exon 1 of 1	6	NM_000682.7	ENSP00000480573.1		P18089

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.11e-7

AC:

AN:

1406106

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31902

American (AMR)

AF:

0.00

AC:

AN:

36446

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24980

East Asian (EAS)

AF:

0.00

AC:

AN:

36406

South Asian (SAS)

AF:

0.0000124

AC:

AN:

80552

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49598

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1082160

Other (OTH)

AF:

0.00

AC:

AN:

58368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.440

Hom.:

2779

Bravo

AF:

0.00000378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ADRA2B-related disorder

Benign:1

Mar 17, 2020

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

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

PhyloP100

1.5

Splicing

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

Publications

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2-96115238-CTCCTCCTCT-CTCCTCCTCTTCCTCCTCT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over