rs3788277

Variant names:

• chr22-17198659-C-G
• rs3788277
• NM_001282225.2:c.753+4904G>C

Variant summary

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

The NM_001282225.2(ADA2):​c.753+4904G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.049 in 152,238 control chromosomes in the GnomAD database, including 235 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 0.049 (235 hom., cov: 32)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: ADA2 NM_001282225.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.604
• 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

LOC107985573 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.125 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.753+4904G>C		intron	N/A	NP_001269154.1	Q9NZK5-1
	ADA2	NM_001282226.2		c.753+4904G>C		intron	N/A	NP_001269155.1	Q9NZK5-1
	ADA2	NM_001282227.2		c.627+4904G>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.753+4904G>C		intron	N/A	ENSP00000382731.2	Q9NZK5-1
	ADA2	ENST00000262607.3	TSL:1	c.753+4904G>C		intron	N/A	ENSP00000262607.2	Q9NZK5-1
	ADA2	ENST00000885359.1		c.870+504G>C		intron	N/A	ENSP00000555418.1

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7447 AN: 152078 Hom.: 233 Cov.: 32

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.0286

Gnomad AMR AF: 0.0903

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.0222

Gnomad FIN AF: 0.0865

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0428

Gnomad OTH AF: 0.0449

GnomAD4 exome AF: 0.0714 AC: 3 AN: 42 Hom.: 0 Cov.: 0 AF XY: 0.100 AC XY: 3 AN XY: 30

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.107 AC: 3 AN: 28

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0490 AC: 7458 AN: 152196 Hom.: 235 Cov.: 32 AF XY: 0.0510 AC XY: 3793 AN XY: 74396

African (AFR) AF: 0.0308 AC: 1278 AN: 41542

American (AMR) AF: 0.0907 AC: 1386 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0130 AC: 45 AN: 3472

East Asian (EAS) AF: 0.133 AC: 687 AN: 5150

South Asian (SAS) AF: 0.0222 AC: 107 AN: 4822

European-Finnish (FIN) AF: 0.0865 AC: 918 AN: 10608

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0428 AC: 2908 AN: 68004

Other (OTH) AF: 0.0454 AC: 96 AN: 2116

Alfa AF: 0.0463 Hom.: 23

Bravo AF: 0.0510

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.96
DANN	Benign	0.74
PhyloP100		-0.60
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: rs3788277; hg19: chr22-17679549;