rs58754958

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001282225.2(ADA2):c.1442+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,607,306 control chromosomes in the GnomAD database, including 80,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6310 hom., cov: 33)

Exomes 𝑓: 0.31 ( 74668 hom. )

Consequence

ADA2
NM_001282225.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.00200

Publications

5 publications found

Variant links:

Genes affected

ADA2 (HGNC:1839): (adenosine deaminase 2) This gene encodes a member of a subfamily of the adenosine deaminase protein family. The encoded protein is one of two adenosine deaminases found in humans, which regulate levels of the signaling molecule, adenosine. The encoded protein is secreted from monocytes undergoing differentiation and may regulate cell proliferation and differentiation. This gene may be responsible for some of the phenotypic features associated with cat eye syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

ADA2 Gene-Disease associations (from GenCC):

deficiency of adenosine deaminase 2
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
vasculitis due to ADA2 deficiency
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
polyarteritis nodosa
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
Sneddon syndrome
Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
Diamond-Blackfan anemia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ADA2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 22-17181809-A-G is Benign according to our data. Variant chr22-17181809-A-G is described in ClinVar as Benign. ClinVar VariationId is 402526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADA2	NM_001282225.2 link	c.1442+11T>C		intron_variant	Intron 9 of 9	ENST00000399837.8	NP_001269154.1	Q9NZK5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADA2	ENST00000399837.8 link	c.1442+11T>C		intron_variant	Intron 9 of 9	1	NM_001282225.2	ENSP00000382731.2		Q9NZK5-1

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42048

AN:

152032

Hom.:

6312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.0511

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.335

Gnomad MID

AF:

0.303

Gnomad NFE

AF:

0.339

Gnomad OTH

AF:

0.302

GnomAD2 exomes

AF:

0.256

AC:

64054

AN:

250578

AF XY:

0.258

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.151

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.0474

Gnomad FIN exome

AF:

0.324

Gnomad NFE exome

AF:

0.334

Gnomad OTH exome

AF:

0.271

GnomAD4 exome

AF:

0.311

AC:

453108

AN:

1455156

Hom.:

74668

Cov.:

AF XY:

0.309

AC XY:

223535

AN XY:

724322

show subpopulations

African (AFR)

AF:

0.213

AC:

7103

AN:

33364

American (AMR)

AF:

0.158

AC:

7049

AN:

44678

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

7390

AN:

26042

East Asian (EAS)

AF:

0.0516

AC:

2050

AN:

39696

South Asian (SAS)

AF:

0.172

AC:

14849

AN:

86082

European-Finnish (FIN)

AF:

0.320

AC:

17058

AN:

53384

Middle Eastern (MID)

AF:

0.316

AC:

1548

AN:

4896

European-Non Finnish (NFE)

AF:

0.342

AC:

378338

AN:

1106930

Other (OTH)

AF:

0.295

AC:

17723

AN:

60084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

13528

27056

40585

54113

67641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11892

23784

35676

47568

59460

<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:

0.276

AC:

42052

AN:

152150

Hom.:

6310

Cov.:

AF XY:

0.270

AC XY:

20094

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.223

AC:

9253

AN:

41542

American (AMR)

AF:

0.214

AC:

3280

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.278

AC:

965

AN:

3468

East Asian (EAS)

AF:

0.0513

AC:

265

AN:

5170

South Asian (SAS)

AF:

0.164

AC:

790

AN:

4826

European-Finnish (FIN)

AF:

0.335

AC:

3546

AN:

10596

Middle Eastern (MID)

AF:

0.291

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.339

AC:

23031

AN:

67936

Other (OTH)

AF:

0.298

AC:

631

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1528

3056

4585

6113

7641

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<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:

0.303

Hom.:

3517

Bravo

AF:

0.264

Asia WGS

AF:

0.113

AC:

391

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

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 33% of patients studied by a panel of primary immunodeficiencies. Number of patients: 32. Only high quality variants are reported. -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

May 10, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Vasculitis due to ADA2 deficiency

Benign:1

Feb 03, 2025

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

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.15

(source)

DANN

Benign

0.63

PhyloP100

0.0020

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