rs362129

Variant names:

• chr22-17209519-G-A
• rs362129
• NM_001282225.2:c.159C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-17209519-G-A
• chr22-17209519-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6 O:1
• Conservation: PhyloP100: -1.11
• Publications: 23 publications found

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

ACMG classification

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	c.159C>T	p.Asn53Asn	synonymous_variant	Exon 2 of 10	ENST00000399837.8	NP_001269154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADA2	ENST00000399837.8	c.159C>T	p.Asn53Asn	synonymous_variant	Exon 2 of 10	1	NM_001282225.2	ENSP00000382731.2

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65657 AN: 151766 Hom.: 15363 Cov.: 31

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

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.: 64 AF XY: 0.500 AC XY: 363519 AN XY: 727186

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

GnomAD4 genome AF: 0.432 AC: 65651 AN: 151884 Hom.: 15355 Cov.: 31 AF XY: 0.424 AC XY: 31487 AN XY: 74194

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

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:6 Other:1

Revision: criteria provided, multiple submitters, no conflicts

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:1 Other: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
DANN	Benign	0.83
PhyloP100		-1.1
PromoterAI		0.012	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs362129; hg19: chr22-17690409; COSMIC: COSV52831513; COSMIC: COSV52831513;