rs58754958

chr22-17181809-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001282225.2(ADA2):c.1442+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,607,306 control chromosomes in the GnomAD database, including 80,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6310 hom., cov: 33)
  • Exomes 𝑓: 0.31 (74668 hom.)
• Consequence: ADA2 NM_001282225.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.00200

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-17181809-A-G is Benign according to our data. Variant chr22-17181809-A-G is described in ClinVar as [Benign]. Clinvar id is 402526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17181809-A-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADA2	NM_001282225.2	c.1442+11T>C		intron_variant		ENST00000399837.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADA2	ENST00000399837.8	c.1442+11T>C		intron_variant		1	NM_001282225.2	P1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42048 AN: 152032 Hom.: 6312 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.0511

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.302

GnomAD3 exomes AF: 0.256 AC: 64054 AN: 250578 Hom.: 9560 AF XY: 0.258 AC XY: 34879 AN XY: 135408

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.0474

Gnomad SAS exome AF: 0.168

Gnomad FIN exome AF: 0.324

Gnomad NFE exome AF: 0.334

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.311 AC: 453108 AN: 1455156 Hom.: 74668 Cov.: 31 AF XY: 0.309 AC XY: 223535 AN XY: 724322

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.284

Gnomad4 EAS exome AF: 0.0516

Gnomad4 SAS exome AF: 0.172

Gnomad4 FIN exome AF: 0.320

Gnomad4 NFE exome AF: 0.342

Gnomad4 OTH exome AF: 0.295

GnomAD4 genome AF: 0.276 AC: 42052 AN: 152150 Hom.: 6310 Cov.: 33 AF XY: 0.270 AC XY: 20094 AN XY: 74382

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.0513

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.298

Alfa AF: 0.318 Hom.: 2436

Bravo AF: 0.264

Asia WGS AF: 0.113 AC: 391 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

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	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 33% of patients studied by a panel of primary immunodeficiencies. Number of patients: 32. Only high quality variants are reported. -
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	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Vasculitis due to ADA2 deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.15
Dann	Benign	0.63

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: rs58754958; hg19: chr22-17662699; COSMIC: COSV52831802; COSMIC: COSV52831802;