rs3788277

Positions:

• chr22-17198659-C-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADA2	NM_001282225.2	c.753+4904G>C		intron_variant		ENST00000399837.8	NP_001269154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADA2	ENST00000399837.8	c.753+4904G>C		intron_variant		1	NM_001282225.2	ENSP00000382731.2

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

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.0308

Gnomad4 AMR AF: 0.0907

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.133

Gnomad4 SAS AF: 0.0222

Gnomad4 FIN AF: 0.0865

Gnomad4 NFE AF: 0.0428

Gnomad4 OTH AF: 0.0454

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.96
DANN	Benign	0.74

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: rs3788277; hg19: chr22-17679549;