NM_001111.5:c.2682G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001111.5(ADAR):c.2682G>A(p.Val894Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,611,136 control chromosomes in the GnomAD database, including 68,238 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.29 ( 6515 hom., cov: 32)

Exomes 𝑓: 0.29 ( 61723 hom. )

Consequence

ADAR
NM_001111.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.386

Publications

30 publications found

Variant links:

Genes affected

ADAR (HGNC:225): (adenosine deaminase RNA specific) This gene encodes the enzyme responsible for RNA editing by site-specific deamination of adenosines. This enzyme destabilizes double-stranded RNA through conversion of adenosine to inosine. Mutations in this gene have been associated with dyschromatosis symmetrica hereditaria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

ADAR Gene-Disease associations (from GenCC):

Aicardi-Goutieres syndrome
Inheritance: AD, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
dyschromatosis symmetrica hereditaria
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), G2P
Aicardi-Goutieres syndrome 6
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
familial infantile bilateral striatal necrosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Leigh syndrome
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ADAR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 1-154589449-C-T is Benign according to our data. Variant chr1-154589449-C-T is described in ClinVar as Benign. ClinVar VariationId is 257474.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.386 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAR	NM_001111.5 link	c.2682G>A	p.Val894Val	synonymous_variant	Exon 9 of 15	ENST00000368474.9	NP_001102.3	P55265-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAR	ENST00000368474.9 link	c.2682G>A	p.Val894Val	synonymous_variant	Exon 9 of 15	1	NM_001111.5	ENSP00000357459.4		P55265-1

Frequencies

GnomAD3 genomes

AF:

0.291

AC:

44293

AN:

151998

Hom.:

6504

Cov.:

show subpopulations

Gnomad AFR

AF:

0.303

Gnomad AMI

AF:

0.336

Gnomad AMR

AF:

0.240

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.294

Gnomad OTH

AF:

0.295

GnomAD2 exomes

AF:

0.271

AC:

68087

AN:

251046

AF XY:

0.274

show subpopulations

Gnomad AFR exome

AF:

0.305

Gnomad AMR exome

AF:

0.165

Gnomad ASJ exome

AF:

0.280

Gnomad EAS exome

AF:

0.282

Gnomad FIN exome

AF:

0.336

Gnomad NFE exome

AF:

0.292

Gnomad OTH exome

AF:

0.284

GnomAD4 exome

AF:

0.288

AC:

420437

AN:

1459020

Hom.:

61723

Cov.:

AF XY:

0.286

AC XY:

207334

AN XY:

726010

show subpopulations

African (AFR)

AF:

0.304

AC:

10180

AN:

33434

American (AMR)

AF:

0.175

AC:

7812

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

7384

AN:

26118

East Asian (EAS)

AF:

0.268

AC:

10644

AN:

39688

South Asian (SAS)

AF:

0.233

AC:

20044

AN:

86204

European-Finnish (FIN)

AF:

0.330

AC:

17585

AN:

53368

Middle Eastern (MID)

AF:

0.266

AC:

1528

AN:

5754

European-Non Finnish (NFE)

AF:

0.295

AC:

327499

AN:

1109438

Other (OTH)

AF:

0.295

AC:

17761

AN:

60294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

14736

29473

44209

58946

73682

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10778

21556

32334

43112

53890

<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:

0.291

AC:

44337

AN:

152116

Hom.:

6515

Cov.:

AF XY:

0.289

AC XY:

21497

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.304

AC:

12601

AN:

41482

American (AMR)

AF:

0.240

AC:

3667

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.264

AC:

914

AN:

3468

East Asian (EAS)

AF:

0.287

AC:

1485

AN:

5166

South Asian (SAS)

AF:

0.225

AC:

1088

AN:

4826

European-Finnish (FIN)

AF:

0.339

AC:

3580

AN:

10558

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.294

AC:

19979

AN:

67994

Other (OTH)

AF:

0.301

AC:

635

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1653

3306

4958

6611

8264

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.291

Hom.:

10183

Bravo

AF:

0.284

Asia WGS

AF:

0.276

AC:

959

AN:

3478

EpiCase

AF:

0.291

EpiControl

AF:

0.297

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 46% of patients studied by a panel of primary immunodeficiencies. Number of patients: 44. Only high quality variants are reported. -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Aug 15, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 31423758) -

Aicardi-Goutieres syndrome 6

Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Symmetrical dyschromatosis of extremities;C3539013:Aicardi-Goutieres syndrome 6

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Symmetrical dyschromatosis of extremities

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

9.5

(source)

DANN

Benign

0.76

PhyloP100

0.39

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

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