rs777404100
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001282225.2(ADA2):āc.83T>Cā(p.Leu28Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001282225.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADA2 | NM_001282225.2 | c.83T>C | p.Leu28Pro | missense_variant | 2/10 | ENST00000399837.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADA2 | ENST00000399837.8 | c.83T>C | p.Leu28Pro | missense_variant | 2/10 | 1 | NM_001282225.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251174Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135812
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461878Hom.: 0 Cov.: 34 AF XY: 0.00000825 AC XY: 6AN XY: 727238
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152156Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74338
ClinVar
Submissions by phenotype
Sneddon syndrome;C3887654:Vasculitis due to ADA2 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Dec 27, 2021 | - - |
Vasculitis due to ADA2 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ADA2 protein function. ClinVar contains an entry for this variant (Variation ID: 474909). This variant has not been reported in the literature in individuals affected with ADA2-related conditions. This variant is present in population databases (rs777404100, gnomAD 0.01%). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 28 of the ADA2 protein (p.Leu28Pro). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at