NM_001282225.2:c.159C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001282225.2(ADA2):c.159C>T(p.Asn53Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,613,674 control chromosomes in the GnomAD database, including 205,484 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 15355 hom., cov: 31)

Exomes 𝑓: 0.50 ( 190129 hom. )

Consequence

ADA2
NM_001282225.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -1.11

Publications

23 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 22-17209519-G-A is Benign according to our data. Variant chr22-17209519-G-A is described in ClinVar as Benign. ClinVar VariationId is 402529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.11 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.53 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADA2	NM_001282225.2 link	c.159C>T	p.Asn53Asn	synonymous_variant	Exon 2 of 10	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.159C>T	p.Asn53Asn	synonymous_variant	Exon 2 of 10	1	NM_001282225.2	ENSP00000382731.2		Q9NZK5-1

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65657

AN:

151766

Hom.:

15363

Cov.:

show subpopulations

Gnomad AFR

AF:

0.301

Gnomad AMI

AF:

0.484

Gnomad AMR

AF:

0.393

Gnomad ASJ

AF:

0.588

Gnomad EAS

AF:

0.0741

Gnomad SAS

AF:

0.412

Gnomad FIN

AF:

0.470

Gnomad MID

AF:

0.513

Gnomad NFE

AF:

0.535

Gnomad OTH

AF:

0.451

GnomAD2 exomes

AF:

0.433

AC:

108735

AN:

251226

AF XY:

0.445

show subpopulations

Gnomad AFR exome

AF:

0.300

Gnomad AMR exome

AF:

0.294

Gnomad ASJ exome

AF:

0.574

Gnomad EAS exome

AF:

0.0655

Gnomad FIN exome

AF:

0.478

Gnomad NFE exome

AF:

0.531

Gnomad OTH exome

AF:

0.480

GnomAD4 exome

AF:

0.501

AC:

732453

AN:

1461790

Hom.:

190129

Cov.:

AF XY:

0.500

AC XY:

363519

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.296

AC:

9902

AN:

33480

American (AMR)

AF:

0.303

AC:

13551

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.580

AC:

15170

AN:

26136

East Asian (EAS)

AF:

0.0877

AC:

3480

AN:

39700

South Asian (SAS)

AF:

0.426

AC:

36743

AN:

86254

European-Finnish (FIN)

AF:

0.484

AC:

25851

AN:

53414

Middle Eastern (MID)

AF:

0.475

AC:

2738

AN:

5760

European-Non Finnish (NFE)

AF:

0.536

AC:

595667

AN:

1111940

Other (OTH)

AF:

0.486

AC:

29351

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

22152

44303

66455

88606

110758

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

16592

33184

49776

66368

82960

<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:

0.432

AC:

65651

AN:

151884

Hom.:

15355

Cov.:

AF XY:

0.424

AC XY:

31487

AN XY:

74194

show subpopulations

African (AFR)

AF:

0.300

AC:

12442

AN:

41420

American (AMR)

AF:

0.392

AC:

5961

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.588

AC:

2042

AN:

3470

East Asian (EAS)

AF:

0.0741

AC:

383

AN:

5170

South Asian (SAS)

AF:

0.411

AC:

1973

AN:

4802

European-Finnish (FIN)

AF:

0.470

AC:

4957

AN:

10536

Middle Eastern (MID)

AF:

0.520

AC:

153

AN:

294

European-Non Finnish (NFE)

AF:

0.535

AC:

36353

AN:

67958

Other (OTH)

AF:

0.448

AC:

947

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1765

3530

5295

7060

8825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

614

1228

1842

2456

3070

<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:

0.496

Hom.:

79789

Bravo

AF:

0.416

Asia WGS

AF:

0.260

AC:

905

AN:

3478

EpiCase

AF:

0.540

EpiControl

AF:

0.542

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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 -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

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 60% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:1Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

GenomeConnect, ClinGen

Significance:not provided

Review Status:no classification provided

Collection Method:phenotyping only

Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

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

-0.87

CADD

Benign

0.43

(source)

DANN

Benign

0.83

PhyloP100

-1.1

PromoterAI

0.012

Neutral

(source)

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