rs373797039
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_001282225.2(ADA2):āc.1386T>Cā(p.Ile462=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,614,116 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: š 0.00048 ( 0 hom., cov: 33)
Exomes š: 0.000063 ( 0 hom. )
Consequence
ADA2
NM_001282225.2 synonymous
NM_001282225.2 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.998
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 Likely_benign. Variant got -4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
?
Variant 22-17181876-A-G is Benign according to our data. Variant chr22-17181876-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 474906.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}. Variant chr22-17181876-A-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-0.998 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADA2 | NM_001282225.2 | c.1386T>C | p.Ile462= | synonymous_variant | 9/10 | ENST00000399837.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADA2 | ENST00000399837.8 | c.1386T>C | p.Ile462= | synonymous_variant | 9/10 | 1 | NM_001282225.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000480 AC: 73AN: 152182Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000437 AC: 11AN: 251456Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135896
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GnomAD4 exome AF: 0.0000629 AC: 92AN: 1461816Hom.: 0 Cov.: 33 AF XY: 0.0000674 AC XY: 49AN XY: 727208
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GnomAD4 genome ? AF: 0.000479 AC: 73AN: 152300Hom.: 0 Cov.: 33 AF XY: 0.000524 AC XY: 39AN XY: 74474
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:3
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Autoinflammatory syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Jul 28, 2020 | - - |
Vasculitis due to ADA2 deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | ADA2: BP4, BP7 - |
ADA2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 01, 2022 | 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
Splicing
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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