NM_001282225.2:c.660C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001282225.2(ADA2):c.660C>T(p.Tyr220Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000948 in 1,613,894 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 6 hom. )

Consequence

ADA2
NM_001282225.2 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0130

Publications

2 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=-0.58).

BP6

Variant 22-17203656-G-A is Benign according to our data. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17203656-G-A is described in CliVar as Benign/Likely_benign. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.013 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00454 (691/152332) while in subpopulation AFR AF = 0.0145 (605/41584). AF 95% confidence interval is 0.0136. There are 6 homozygotes in GnomAd4. There are 333 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADA2	NM_001282225.2 link	c.660C>T	p.Tyr220Tyr	synonymous_variant	Exon 4 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.660C>T	p.Tyr220Tyr	synonymous_variant	Exon 4 of 10	1	NM_001282225.2	ENSP00000382731.2		Q9NZK5-1

Frequencies

GnomAD3 genomes

AF:

0.00455

AC:

692

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00360

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00135

AC:

340

AN:

251458

AF XY:

0.000942

show subpopulations

Gnomad AFR exome

AF:

0.0152

Gnomad AMR exome

AF:

0.000867

Gnomad ASJ exome

AF:

0.00476

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000574

AC:

839

AN:

1461562

Hom.:

Cov.:

AF XY:

0.000490

AC XY:

356

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.0158

AC:

530

AN:

33466

American (AMR)

AF:

0.00112

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00364

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000348

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.0000639

AC:

AN:

1111728

Other (OTH)

AF:

0.00144

AC:

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

100

150

200

250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00454

AC:

691

AN:

152332

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0145

AC:

605

AN:

41584

American (AMR)

AF:

0.00360

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00518

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68036

Other (OTH)

AF:

0.00473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

102

136

170

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:

0.00464

Hom.:

Bravo

AF:

0.00530

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Aug 30, 2019

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

ADA2: BP4, BP7, BS1, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Vasculitis due to ADA2 deficiency

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autoinflammatory syndrome

Benign:1

Jan 27, 2021

Genome Diagnostics Laboratory, The Hospital for Sick Children

Significance:Likely 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

-0.58

CADD

Benign

1.1

(source)

DANN

Benign

0.59

PhyloP100

0.013

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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