Variant rs7289170 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001282225.2(ADA2):c.1359T>C(p.Tyr453=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,613,476 control chromosomes in the GnomAD database, including 80,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6385 hom., cov: 32)

Exomes 𝑓: 0.31 ( 73665 hom. )

Consequence

ADA2
NM_001282225.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.458

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 22-17181903-A-G is Benign according to our data. Variant chr22-17181903-A-G is described in ClinVar as [Benign]. Clinvar id is 402527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr22-17181903-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.458 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADA2	NM_001282225.2 linkuse as main transcript	c.1359T>C	p.Tyr453=	synonymous_variant	9/10	ENST00000399837.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADA2	ENST00000399837.8 linkuse as main transcript	c.1359T>C	p.Tyr453=	synonymous_variant	9/10	1	NM_001282225.2	P1	Q9NZK5-1

Frequencies

GnomAD3 genomes

AF:

0.279

AC:

42457

AN:

151988

Hom.:

6387

Cov.:

show subpopulations

Gnomad AFR

AF:

0.240

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.215

Gnomad ASJ

AF:

0.275

Gnomad EAS

AF:

0.0513

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.334

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.301

GnomAD3 exomes

AF:

0.256

AC:

64305

AN:

251404

Hom.:

9566

AF XY:

0.258

AC XY:

35021

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.233

Gnomad AMR exome

AF:

0.152

Gnomad ASJ exome

AF:

0.283

Gnomad EAS exome

AF:

0.0475

Gnomad SAS exome

AF:

0.168

Gnomad FIN exome

AF:

0.324

Gnomad NFE exome

AF:

0.332

Gnomad OTH exome

AF:

0.269

GnomAD4 exome

AF:

0.309

AC:

452265

AN:

1461370

Hom.:

73665

Cov.:

AF XY:

0.307

AC XY:

222977

AN XY:

727028

show subpopulations

Gnomad4 AFR exome

AF:

0.231

Gnomad4 AMR exome

AF:

0.159

Gnomad4 ASJ exome

AF:

0.282

Gnomad4 EAS exome

AF:

0.0517

Gnomad4 SAS exome

AF:

0.173

Gnomad4 FIN exome

AF:

0.319

Gnomad4 NFE exome

AF:

0.339

Gnomad4 OTH exome

AF:

0.293

GnomAD4 genome

AF:

0.279

AC:

42470

AN:

152106

Hom.:

6385

Cov.:

AF XY:

0.273

AC XY:

20329

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.240

Gnomad4 AMR

AF:

0.215

Gnomad4 ASJ

AF:

0.275

Gnomad4 EAS

AF:

0.0514

Gnomad4 SAS

AF:

0.164

Gnomad4 FIN

AF:

0.334

Gnomad4 NFE

AF:

0.335

Gnomad4 OTH

AF:

0.297

Alfa

AF:

0.313

Hom.:

4030

Bravo

AF:

0.268

Asia WGS

AF:

0.114

AC:

396

AN:

3478

EpiCase

AF:

0.333

EpiControl

AF:

0.329

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 34% of patients studied by a panel of primary immunodeficiencies. Number of patients: 33. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

not provided

Benign:1Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
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. This variant was reported in an individual referred for clinical diagnostic genetic testing. -

Vasculitis due to ADA2 deficiency

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

0.27

DANN

Benign

0.22

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