Variant 22-17181789-C-T details in Genebe, Genetics Data Aggregator

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+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,578,648 control chromosomes in the GnomAD database, including 73,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6030 hom., cov: 33)

Exomes 𝑓: 0.30 ( 67210 hom. )

Consequence

ADA2
NM_001282225.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.36

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=-0.9).

BP6

Variant 22-17181789-C-T is Benign according to our data. Variant chr22-17181789-C-T is described in ClinVar as [Benign]. Clinvar id is 1266748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 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.1442+31G>A		intron_variant		ENST00000399837.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADA2	ENST00000399837.8 linkuse as main transcript	c.1442+31G>A		intron_variant		1	NM_001282225.2	P1	Q9NZK5-1

Frequencies

GnomAD3 genomes

AF:

0.271

AC:

41195

AN:

152008

Hom.:

6033

Cov.:

show subpopulations

Gnomad AFR

AF:

0.230

Gnomad AMI

AF:

0.225

Gnomad AMR

AF:

0.206

Gnomad ASJ

AF:

0.255

Gnomad EAS

AF:

0.0512

Gnomad SAS

AF:

0.156

Gnomad FIN

AF:

0.324

Gnomad MID

AF:

0.288

Gnomad NFE

AF:

0.328

Gnomad OTH

AF:

0.291

GnomAD3 exomes

AF:

0.247

AC:

61195

AN:

247978

Hom.:

8757

AF XY:

0.248

AC XY:

33277

AN XY:

133934

show subpopulations

Gnomad AFR exome

AF:

0.224

Gnomad AMR exome

AF:

0.145

Gnomad ASJ exome

AF:

0.263

Gnomad EAS exome

AF:

0.0475

Gnomad SAS exome

AF:

0.161

Gnomad FIN exome

AF:

0.311

Gnomad NFE exome

AF:

0.322

Gnomad OTH exome

AF:

0.261

GnomAD4 exome

AF:

0.299

AC:

425832

AN:

1426520

Hom.:

67210

Cov.:

AF XY:

0.296

AC XY:

210569

AN XY:

711554

show subpopulations

Gnomad4 AFR exome

AF:

0.220

Gnomad4 AMR exome

AF:

0.153

Gnomad4 ASJ exome

AF:

0.262

Gnomad4 EAS exome

AF:

0.0514

Gnomad4 SAS exome

AF:

0.165

Gnomad4 FIN exome

AF:

0.308

Gnomad4 NFE exome

AF:

0.328

Gnomad4 OTH exome

AF:

0.282

GnomAD4 genome

AF:

0.271

AC:

41206

AN:

152128

Hom.:

6030

Cov.:

AF XY:

0.265

AC XY:

19688

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.229

Gnomad4 AMR

AF:

0.206

Gnomad4 ASJ

AF:

0.255

Gnomad4 EAS

AF:

0.0513

Gnomad4 SAS

AF:

0.158

Gnomad4 FIN

AF:

0.324

Gnomad4 NFE

AF:

0.328

Gnomad4 OTH

AF:

0.289

Alfa

AF:

0.225

Hom.:

807

Bravo

AF:

0.260

Asia WGS

AF:

0.109

AC:

377

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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. -

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

-0.90

Cadd

Benign

0.075

Dann

Benign

0.76

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