22-17182027-G-C

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.1240-5C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,605,842 control chromosomes in the GnomAD database, including 75,008 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5979 hom., cov: 32)

Exomes 𝑓: 0.30 ( 69029 hom. )

Consequence

ADA2
NM_001282225.2 splice_region, intron

Scores

Splicing: ADA: 0.0002144

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7O:1

Conservation

PhyloP100: -0.278

Publications

9 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)
Sneddon syndrome
Inheritance: AD, AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
polyarteritis nodosa
Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
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=-0.87).

BP6

Variant 22-17182027-G-C is Benign according to our data. Variant chr22-17182027-G-C is described in ClinVar as Benign. ClinVar VariationId is 402528.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282225.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADA2	NM_001282225.2	MANE Select	c.1240-5C>G	splice_region intron	N/A	NP_001269154.1	Q9NZK5-1
ADA2	NM_001282226.2		c.1240-5C>G	splice_region intron	N/A	NP_001269155.1	Q9NZK5-1
ADA2	NM_001282227.2		c.1114-5C>G	splice_region intron	N/A	NP_001269156.1	B4E3Q4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ADA2	ENST00000399837.8	TSL:1 MANE Select	c.1240-5C>G	splice_region intron	N/A	ENSP00000382731.2	Q9NZK5-1
ADA2	ENST00000262607.3	TSL:1	c.1240-5C>G	splice_region intron	N/A	ENSP00000262607.2	Q9NZK5-1
ADA2	ENST00000885359.1		c.1357-5C>G	splice_region intron	N/A	ENSP00000555418.1

Frequencies

GnomAD3 genomes

AF:

0.270

AC:

40994

AN:

151910

Hom.:

5983

Cov.:

show subpopulations

Gnomad AFR

AF:

0.229

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.252

Gnomad EAS

AF:

0.0511

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.326

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.326

Gnomad OTH

AF:

0.291

GnomAD2 exomes

AF:

0.246

AC:

61385

AN:

249176

AF XY:

0.248

show subpopulations

Gnomad AFR exome

AF:

0.223

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.258

Gnomad EAS exome

AF:

0.0475

Gnomad FIN exome

AF:

0.314

Gnomad NFE exome

AF:

0.321

Gnomad OTH exome

AF:

0.259

GnomAD4 exome

AF:

0.299

AC:

434998

AN:

1453812

Hom.:

69029

Cov.:

AF XY:

0.296

AC XY:

214350

AN XY:

723328

show subpopulations

African (AFR)

AF:

0.221

AC:

7388

AN:

33362

American (AMR)

AF:

0.152

AC:

6786

AN:

44530

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

6683

AN:

25872

East Asian (EAS)

AF:

0.0515

AC:

2041

AN:

39668

South Asian (SAS)

AF:

0.165

AC:

14201

AN:

85956

European-Finnish (FIN)

AF:

0.310

AC:

16501

AN:

53290

Middle Eastern (MID)

AF:

0.307

AC:

1759

AN:

5722

European-Non Finnish (NFE)

AF:

0.328

AC:

362743

AN:

1105318

Other (OTH)

AF:

0.281

AC:

16896

AN:

60094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

12908

25816

38723

51631

64539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11492

22984

34476

45968

57460

<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:

0.270

AC:

41004

AN:

152030

Hom.:

5979

Cov.:

AF XY:

0.264

AC XY:

19604

AN XY:

74306

show subpopulations

African (AFR)

AF:

0.229

AC:

9490

AN:

41466

American (AMR)

AF:

0.206

AC:

3142

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.252

AC:

873

AN:

3470

East Asian (EAS)

AF:

0.0512

AC:

265

AN:

5176

South Asian (SAS)

AF:

0.157

AC:

759

AN:

4822

European-Finnish (FIN)

AF:

0.326

AC:

3451

AN:

10570

Middle Eastern (MID)

AF:

0.279

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.326

AC:

22129

AN:

67948

Other (OTH)

AF:

0.288

AC:

608

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1501

3002

4502

6003

7504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

408

816

1224

1632

2040

<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:

0.221

Hom.:

765

Bravo

AF:

0.259

EpiCase

AF:

0.322

EpiControl

AF:

0.317

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (3)

Vasculitis due to ADA2 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

1.2

(source)

DANN

Benign

0.66

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00021

dbscSNV1_RF

Benign

0.018

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over