Genetic Variant ADARB2:p.Glu300Lys (chr10-1363207-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_018702.4(ADARB2):c.898G>A(p.Glu300Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00564 in 1,473,340 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0058 ( 33 hom. )

Consequence

ADARB2
NM_018702.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.18

Publications

6 publications found

Variant links:

Genes affected

ADARB2 (HGNC:227): (adenosine deaminase RNA specific B2 (inactive)) This gene encodes a member of the double-stranded RNA adenosine deaminase family of RNA-editing enzymes and may play a regulatory role in RNA editing. [provided by RefSeq, Jul 2008]

ADARB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005900234).

BP6

Variant 10-1363207-C-T is Benign according to our data. Variant chr10-1363207-C-T is described in ClinVar as Benign. ClinVar VariationId is 773917.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADARB2	NM_018702.4 link	c.898G>A	p.Glu300Lys	missense_variant	Exon 3 of 10	ENST00000381312.6	NP_061172.1	Q9NS39-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADARB2	ENST00000381312.6 link	c.898G>A	p.Glu300Lys	missense_variant	Exon 3 of 10	1	NM_018702.4	ENSP00000370713.1		Q9NS39-1

Frequencies

GnomAD3 genomes

AF:

0.00394

AC:

598

AN:

151808

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00102

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00597

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00595

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00422

AC:

491

AN:

116234

AF XY:

0.00423

show subpopulations

Gnomad AFR exome

AF:

0.00128

Gnomad AMR exome

AF:

0.00496

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000173

Gnomad FIN exome

AF:

0.00552

Gnomad NFE exome

AF:

0.00567

Gnomad OTH exome

AF:

0.00661

GnomAD4 exome

AF:

0.00584

AC:

7715

AN:

1321424

Hom.:

Cov.:

AF XY:

0.00567

AC XY:

3707

AN XY:

654270

show subpopulations

African (AFR)

AF:

0.000629

AC:

AN:

27028

American (AMR)

AF:

0.00529

AC:

161

AN:

30418

Ashkenazi Jewish (ASJ)

AF:

0.0000888

AC:

AN:

22516

East Asian (EAS)

AF:

0.000102

AC:

AN:

29526

South Asian (SAS)

AF:

0.00196

AC:

140

AN:

71390

European-Finnish (FIN)

AF:

0.00483

AC:

167

AN:

34560

Middle Eastern (MID)

AF:

0.00240

AC:

AN:

5418

European-Non Finnish (NFE)

AF:

0.00662

AC:

6928

AN:

1046654

Other (OTH)

AF:

0.00527

AC:

284

AN:

53914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

484

968

1451

1935

2419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

268

536

804

1072

1340

<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:

0.00394

AC:

598

AN:

151916

Hom.:

Cov.:

AF XY:

0.00378

AC XY:

281

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

41484

American (AMR)

AF:

0.00426

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000389

AC:

AN:

5138

South Asian (SAS)

AF:

0.00269

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00597

AC:

AN:

10550

Middle Eastern (MID)

AF:

0.00

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00595

AC:

404

AN:

67866

Other (OTH)

AF:

0.00427

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

130

163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00376

Hom.:

Bravo

AF:

0.00403

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.00375

AC:

ExAC

AF:

0.00319

AC:

359

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 07, 2018

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

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.25

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.061

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.51

MutationAssessor

Benign

1.2

PhyloP100

3.2

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.33

Sift

Benign

0.11

Sift4G

Benign

0.23

Polyphen

0.64

Vest4

0.23

MVP

0.37

MPC

1.6

ClinPred

0.029

GERP RS

3.3

Varity_R

0.053

gMVP

0.44

Mutation Taster

=91/9

polymorphism

(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