22-17229970-C-T

Variant names:

• chr22-17229970-C-T
• rs9606661
• ENST00000649310.2:c.-46-20247G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000649310.2(ADA2):​c.-46-20247G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 152,164 control chromosomes in the GnomAD database, including 1,284 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.12 (1284 hom., cov: 32)
• Consequence: ADA2 ENST00000649310.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• deficiency of adenosine deaminase 2

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• vasculitis due to ADA2 deficiency

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• Sneddon syndrome

  Inheritance: AD, AR Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• polyarteritis nodosa

  Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
• Diamond-Blackfan anemia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000649310.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADA2	ENST00000649310.2		c.-46-20247G>A		intron	N/A	ENSP00000496839.2	Q9NZK5-1
	ADA2	ENST00000649746.2		c.-421-7869G>A		intron	N/A	ENSP00000497913.2	Q9NZK5-1
	ADA2	ENST00000696197.1		c.-998+193G>A		intron	N/A	ENSP00000512480.1	Q9NZK5-1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18213 AN: 152046 Hom.: 1283 Cov.: 32

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.0648

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.114

Gnomad SAS AF: 0.0462

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.0954

Gnomad OTH AF: 0.116

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.120 AC: 18226 AN: 152164 Hom.: 1284 Cov.: 32 AF XY: 0.118 AC XY: 8806 AN XY: 74396

African (AFR) AF: 0.188 AC: 7815 AN: 41514

American (AMR) AF: 0.0646 AC: 987 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 446 AN: 3468

East Asian (EAS) AF: 0.115 AC: 595 AN: 5178

South Asian (SAS) AF: 0.0471 AC: 227 AN: 4820

European-Finnish (FIN) AF: 0.108 AC: 1139 AN: 10586

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0954 AC: 6485 AN: 68006

Other (OTH) AF: 0.115 AC: 244 AN: 2114

Alfa AF: 0.0987 Hom.: 1190

Bravo AF: 0.122

Asia WGS AF: 0.0790 AC: 274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.7
DANN	Benign	0.67
PhyloP100		-0.17

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9606661; hg19: chr22-17710860;