dbSNP rs58754958: ADA2:c.1442+11T>C (chr22-17181809-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.00200

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 rank	MANE	Protein	UniProt
ADA2	NM_001282225.2 link	c.1442+11T>C		intron_variant	Intron 9 of 9	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.1442+11T>C		intron_variant	Intron 9 of 9	1	NM_001282225.2	ENSP00000382731.2		Q9NZK5-1

Frequencies

GnomAD3 genomes

AF:

0.277

AC:

42048

AN:

152032

Hom.:

6312

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.309

AC XY:

223535

AN XY:

724322

show subpopulations

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.:

AF XY:

0.270

AC XY:

20094

AN XY:

74382

show subpopulations

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:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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 33% of patients studied by a panel of primary immunodeficiencies. Number of patients: 32. 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

- -

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 -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 10, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical 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

-0.88

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over