rs362129

Positions:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: -1.11

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 -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	Protein	UniProt
ADA2	NM_001282225.2 linkuse as main transcript	c.159C>T	p.Asn53=	synonymous_variant	2/10	ENST00000399837.8	NP_001269154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADA2	ENST00000399837.8 linkuse as main transcript	c.159C>T	p.Asn53=	synonymous_variant	2/10	1	NM_001282225.2	ENSP00000382731	P1	Q9NZK5-1

Frequencies

GnomAD3 genomes

AF:

0.433

AC:

65657

AN:

151766

Hom.:

15363

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.500

AC XY:

363519

AN XY:

727186

show subpopulations

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.:

AF XY:

0.424

AC XY:

31487

AN XY:

74194

show subpopulations

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:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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	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 60% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:1Other: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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Vasculitis due to ADA2 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

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

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