rs362129

chr22-17209519-G-Achr22-17209519-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001282225.2(ADA2):c.159C>T(p.Asn53=) 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:5 O:1
• Conservation: PhyloP100: -1.11

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 402529.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17209519-G-A is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
ADA2	NM_001282225.2	c.159C>T	p.Asn53=	synonymous_variant	2/10	ENST00000399837.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADA2	ENST00000399837.8	c.159C>T	p.Asn53=	synonymous_variant	2/10	1	NM_001282225.2	P1

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

GnomAD3 exomes AF: 0.433 AC: 108735 AN: 251226 Hom.: 26111 AF XY: 0.445 AC XY: 60447 AN XY: 135784

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 SAS exome AF: 0.428

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

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.303

Gnomad4 ASJ exome AF: 0.580

Gnomad4 EAS exome AF: 0.0877

Gnomad4 SAS exome AF: 0.426

Gnomad4 FIN exome AF: 0.484

Gnomad4 NFE exome AF: 0.536

Gnomad4 OTH exome AF: 0.486

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

Gnomad4 AFR AF: 0.300

Gnomad4 AMR AF: 0.392

Gnomad4 ASJ AF: 0.588

Gnomad4 EAS AF: 0.0741

Gnomad4 SAS AF: 0.411

Gnomad4 FIN AF: 0.470

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.448

Alfa AF: 0.511 Hom.: 39885

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:5 Other:1

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	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 -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	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. -

Vasculitis due to ADA2 deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Other:1

not provided, no classification provided

phenotyping only

GenomeConnect, ClinGen

-

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.43
Dann	Benign	0.83

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

LitVar

Other links and lift over

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