22-17181701-C-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+119G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 1,072,210 control chromosomes in the GnomAD database, including 43,956 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6004 hom., cov: 32)
  • Exomes 𝑓: 0.28 (37952 hom.)
• Consequence: ADA2 NM_001282225.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.31

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=-0.89).
• BP6: Variant 22-17181701-C-G is Benign according to our data. Variant chr22-17181701-C-G is described in ClinVar as [Benign]. Clinvar id is 1285778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADA2	NM_001282225.2	c.1442+119G>C		intron_variant		ENST00000399837.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADA2	ENST00000399837.8	c.1442+119G>C		intron_variant		1	NM_001282225.2	P1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41083 AN: 151978 Hom.: 6007 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0511

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.290

GnomAD4 exome AF: 0.275 AC: 253243 AN: 920112 Hom.: 37952 Cov.: 12 AF XY: 0.273 AC XY: 130392 AN XY: 477464

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.0515

Gnomad4 SAS exome AF: 0.164

Gnomad4 FIN exome AF: 0.309

Gnomad4 NFE exome AF: 0.309

Gnomad4 OTH exome AF: 0.270

GnomAD4 genome AF: 0.270 AC: 41095 AN: 152098 Hom.: 6004 Cov.: 32 AF XY: 0.264 AC XY: 19644 AN XY: 74330

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.0512

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.326

Gnomad4 OTH AF: 0.287

Alfa AF: 0.300 Hom.: 887

Bravo AF: 0.259

Asia WGS AF: 0.108 AC: 374 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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 33% of patients studied by a panel of primary immunodeficiencies. Number of patients: 32. 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	-0.89
Cadd	Benign	0.57
Dann	Benign	0.58

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: rs11703884; hg19: chr22-17662591;