22-17181586-G-A

Variant names:

• chr22-17181586-G-A
• rs2123599314
• NM_001282225.2:c.1443-10C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001282225.2(ADA2):​c.1443-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000698 in 1,432,210 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: ADA2 NM_001282225.2 intron
• Scores: Splicing: ADA: 0.00003222
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

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.1443-10C>T		intron	N/A	NP_001269154.1	Q9NZK5-1
	ADA2	NM_001282226.2		c.1443-10C>T		intron	N/A	NP_001269155.1	Q9NZK5-1
	ADA2	NM_001282227.2		c.1317-10C>T		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.1443-10C>T		intron	N/A	ENSP00000382731.2	Q9NZK5-1
	ADA2	ENST00000262607.3	TSL:1	c.1443-10C>T		intron	N/A	ENSP00000262607.2	Q9NZK5-1
	ADA2	ENST00000885359.1		c.1560-10C>T		intron	N/A	ENSP00000555418.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.98e-7 AC: 1 AN: 1432210 Hom.: 0 Cov.: 25 AF XY: 0.00000140 AC XY: 1 AN XY: 714324

African (AFR) AF: 0.00 AC: 0 AN: 32796

American (AMR) AF: 0.00 AC: 0 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25968

East Asian (EAS) AF: 0.00 AC: 0 AN: 39552

South Asian (SAS) AF: 0.00 AC: 0 AN: 85624

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5070

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085762

Other (OTH) AF: 0.00 AC: 0 AN: 59358

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.1
DANN	Benign	0.47
PhyloP100		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000032
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.020		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: rs2123599314; hg19: chr22-17662476;