rs770689762
Variant summary
Our verdict is Pathogenic. Variant got 16 ACMG points: 16P and 0B. PM2PM5PP3_StrongPP5_Very_Strong
The NM_001282225.2(ADA2):c.1147G>A(p.Gly383Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000174 in 1,613,800 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G383D) has been classified as Pathogenic.
Frequency
Consequence
NM_001282225.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 16 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADA2 | NM_001282225.2 | c.1147G>A | p.Gly383Ser | missense_variant | 8/10 | ENST00000399837.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADA2 | ENST00000399837.8 | c.1147G>A | p.Gly383Ser | missense_variant | 8/10 | 1 | NM_001282225.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 151978Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251496Hom.: 0 AF XY: 0.0000515 AC XY: 7AN XY: 135922
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461822Hom.: 0 Cov.: 31 AF XY: 0.0000151 AC XY: 11AN XY: 727214
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 151978Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74228
ClinVar
Submissions by phenotype
Vasculitis due to ADA2 deficiency Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 14, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 383 of the ADA2 protein (p.Gly383Ser). This variant is present in population databases (rs770689762, gnomAD 0.008%). This missense change has been observed in individual(s) with deficiency of adenosine deaminase 2 (DADA2) (PMID: 25075847). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as 424G>A (G142S). ClinVar contains an entry for this variant (Variation ID: 189343). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ADA2 protein function. For these reasons, this variant has been classified as Pathogenic. - |
Sneddon syndrome;C3887654:Vasculitis due to ADA2 deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 11, 2022 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Nov 19, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 30645994, 25075847, 34210540, 34004258, 33021335) - |
Sneddon syndrome Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jul 31, 2014 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at