22-17188349-G-A
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_001282225.2(ADA2):c.1071C>T(p.Ala357Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000193 in 1,612,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000092 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00020 ( 0 hom. )
Consequence
ADA2
NM_001282225.2 synonymous
NM_001282225.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.633
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP6
Variant 22-17188349-G-A is Benign according to our data. Variant chr22-17188349-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 474905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.633 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADA2 | NM_001282225.2 | c.1071C>T | p.Ala357Ala | synonymous_variant | 7/10 | ENST00000399837.8 | NP_001269154.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADA2 | ENST00000399837.8 | c.1071C>T | p.Ala357Ala | synonymous_variant | 7/10 | 1 | NM_001282225.2 | ENSP00000382731.2 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152194Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.000374 AC: 94AN: 251136Hom.: 0 AF XY: 0.000287 AC XY: 39AN XY: 135742
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GnomAD4 exome AF: 0.000204 AC: 298AN: 1460730Hom.: 0 Cov.: 31 AF XY: 0.000171 AC XY: 124AN XY: 726760
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GnomAD4 genome AF: 0.0000920 AC: 14AN: 152194Hom.: 0 Cov.: 34 AF XY: 0.0000807 AC XY: 6AN XY: 74348
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Vasculitis due to ADA2 deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 25, 2024 | - - |
Sneddon syndrome;C3887654:Vasculitis due to ADA2 deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 27, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2021 | - - |
ADA2-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 30, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at