Variant 2-96115015-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000682.7(ADRA2B):c.1135G>A(p.Val379Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00262 in 1,613,764 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V379G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 8 hom. )

Consequence

ADRA2B
NM_000682.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 5.02

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011813432).

BP6

Variant 2-96115015-C-T is Benign according to our data. Variant chr2-96115015-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 707066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 299 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADRA2B	NM_000682.7 link	c.1135G>A	p.Val379Ile	missense_variant	1/1	ENST00000620793.2	NP_000673.2	P18089

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADRA2B	ENST00000620793.2 link	c.1135G>A	p.Val379Ile	missense_variant	1/1	6	NM_000682.7	ENSP00000480573.1		P18089

Frequencies

GnomAD3 genomes

AF:

0.00196

AC:

299

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000458

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00222

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00309

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00186

AC:

460

AN:

247858

Hom.:

AF XY:

0.00198

AC XY:

266

AN XY:

134612

show subpopulations

Gnomad AFR exome

AF:

0.000583

Gnomad AMR exome

AF:

0.000813

Gnomad ASJ exome

AF:

0.00558

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000655

Gnomad FIN exome

AF:

0.000326

Gnomad NFE exome

AF:

0.00294

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00269

AC:

3935

AN:

1461438

Hom.:

Cov.:

AF XY:

0.00266

AC XY:

1932

AN XY:

726994

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.00566

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000777

Gnomad4 FIN exome

AF:

0.000206

Gnomad4 NFE exome

AF:

0.00307

Gnomad4 OTH exome

AF:

0.00358

GnomAD4 genome

AF:

0.00196

AC:

299

AN:

152326

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

128

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00222

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00309

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00303

Hom.:

Bravo

AF:

0.00193

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000683

AC:

ESP6500EA

AF:

0.00338

AC:

ExAC

AF:

0.00210

AC:

255

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00376

EpiControl

AF:

0.00344

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Uncertain

0.030

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.036

MetaRNN

Benign

0.012

MetaSVM

Uncertain

0.17

PrimateAI

Uncertain

0.57

Sift4G

Uncertain

0.0030

Polyphen

0.92

Vest4

0.29

MVP

0.43

ClinPred

0.037

GERP RS

4.7

Varity_R

0.071

gMVP

0.77

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over