NM_001282225.2:c.1442+11T>C

Variant names:

• chr22-17181809-A-G
• rs58754958
• NM_001282225.2:c.1442+11T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001282225.2(ADA2):​c.1442+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 1,607,306 control chromosomes in the GnomAD database, including 80,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6310 hom., cov: 33)
  • Exomes 𝑓: 0.31 (74668 hom.)
• Consequence: ADA2 NM_001282225.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.00200
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-17181809-A-G is Benign according to our data. Variant chr22-17181809-A-G is described in ClinVar as Benign. ClinVar VariationId is 402526.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282225.2. 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
	ADA2	NM_001282225.2	MANE Select	c.1442+11T>C		intron	N/A	NP_001269154.1	Q9NZK5-1
	ADA2	NM_001282226.2		c.1442+11T>C		intron	N/A	NP_001269155.1	Q9NZK5-1
	ADA2	NM_001282227.2		c.1316+11T>C		intron	N/A	NP_001269156.1	B4E3Q4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADA2	ENST00000399837.8	TSL:1 MANE Select	c.1442+11T>C		intron	N/A	ENSP00000382731.2	Q9NZK5-1
	ADA2	ENST00000262607.3	TSL:1	c.1442+11T>C		intron	N/A	ENSP00000262607.2	Q9NZK5-1
	ADA2	ENST00000885359.1		c.1559+11T>C		intron	N/A	ENSP00000555418.1

Frequencies

GnomAD3 genomes AF: 0.277 AC: 42048 AN: 152032 Hom.: 6312 Cov.: 33

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.0511

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.302

GnomAD2 exomes AF: 0.256 AC: 64054 AN: 250578 AF XY: 0.258

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.151

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.0474

Gnomad FIN exome AF: 0.324

Gnomad NFE exome AF: 0.334

Gnomad OTH exome AF: 0.271

GnomAD4 exome AF: 0.311 AC: 453108 AN: 1455156 Hom.: 74668 Cov.: 31 AF XY: 0.309 AC XY: 223535 AN XY: 724322

African (AFR) AF: 0.213 AC: 7103 AN: 33364

American (AMR) AF: 0.158 AC: 7049 AN: 44678

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 7390 AN: 26042

East Asian (EAS) AF: 0.0516 AC: 2050 AN: 39696

South Asian (SAS) AF: 0.172 AC: 14849 AN: 86082

European-Finnish (FIN) AF: 0.320 AC: 17058 AN: 53384

Middle Eastern (MID) AF: 0.316 AC: 1548 AN: 4896

European-Non Finnish (NFE) AF: 0.342 AC: 378338 AN: 1106930

Other (OTH) AF: 0.295 AC: 17723 AN: 60084

GnomAD4 genome AF: 0.276 AC: 42052 AN: 152150 Hom.: 6310 Cov.: 33 AF XY: 0.270 AC XY: 20094 AN XY: 74382

African (AFR) AF: 0.223 AC: 9253 AN: 41542

American (AMR) AF: 0.214 AC: 3280 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.278 AC: 965 AN: 3468

East Asian (EAS) AF: 0.0513 AC: 265 AN: 5170

South Asian (SAS) AF: 0.164 AC: 790 AN: 4826

European-Finnish (FIN) AF: 0.335 AC: 3546 AN: 10596

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.339 AC: 23031 AN: 67936

Other (OTH) AF: 0.298 AC: 631 AN: 2116

Alfa AF: 0.303 Hom.: 3517

Bravo AF: 0.264

Asia WGS AF: 0.113 AC: 391 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	not provided (2)
-	-	1	Vasculitis due to ADA2 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.15
DANN	Benign	0.63
PhyloP100		0.0020
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs58754958; hg19: chr22-17662699; COSMIC: COSV52831802; COSMIC: COSV52831802;