rs2231487
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001282225.2(ADA2):c.660C>T(p.Tyr220=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000948 in 1,613,894 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0045 ( 6 hom., cov: 32)
Exomes 𝑓: 0.00057 ( 6 hom. )
Consequence
ADA2
NM_001282225.2 synonymous
NM_001282225.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0130
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
?
Variant 22-17203656-G-A is Benign according to our data. Variant chr22-17203656-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 541739.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.013 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00454 (691/152332) while in subpopulation AFR AF= 0.0145 (605/41584). AF 95% confidence interval is 0.0136. There are 6 homozygotes in gnomad4. There are 333 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADA2 | NM_001282225.2 | c.660C>T | p.Tyr220= | synonymous_variant | 4/10 | ENST00000399837.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADA2 | ENST00000399837.8 | c.660C>T | p.Tyr220= | synonymous_variant | 4/10 | 1 | NM_001282225.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00455 AC: 692AN: 152214Hom.: 6 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
692
AN:
152214
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00135 AC: 340AN: 251458Hom.: 1 AF XY: 0.000942 AC XY: 128AN XY: 135914
GnomAD3 exomes
AF:
AC:
340
AN:
251458
Hom.:
AF XY:
AC XY:
128
AN XY:
135914
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000574 AC: 839AN: 1461562Hom.: 6 Cov.: 32 AF XY: 0.000490 AC XY: 356AN XY: 727116
GnomAD4 exome
AF:
AC:
839
AN:
1461562
Hom.:
Cov.:
32
AF XY:
AC XY:
356
AN XY:
727116
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00454 AC: 691AN: 152332Hom.: 6 Cov.: 32 AF XY: 0.00447 AC XY: 333AN XY: 74488
GnomAD4 genome
?
AF:
AC:
691
AN:
152332
Hom.:
Cov.:
32
AF XY:
AC XY:
333
AN XY:
74488
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
5
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 30, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | ADA2: BP4, BP7, BS1, BS2 - |
Vasculitis due to ADA2 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 26, 2024 | - - |
Autoinflammatory syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jan 27, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at