Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000792233 | SCV000931514 | uncertain significance | Spondyloenchondrodysplasia with immune dysregulation | 2022-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 269 of the ACP5 protein (p.Arg269Trp). This variant is present in population databases (rs199986980, gnomAD 0.04%). This missense change has been observed in individual(s) with systemic lupus erythematosus (PMID: 27390188). ClinVar contains an entry for this variant (Variation ID: 639443). 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 not expected to disrupt ACP5 protein function. Experimental studies have shown that this missense change affects ACP5 function (PMID: 27390188). 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. |
Gene |
RCV002280141 | SCV002568564 | uncertain significance | not provided | 2022-08-26 | criteria provided, single submitter | clinical testing | Reported in association with systemic lupus erythematosus (SLE); however, detailed clinical information was not provided (An et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Published functional studies demonstrate a damaging effect as this variant results in decreased tartrate-resistant acid phosphatase (TRAP) activity compared to wild-type in an in vitro assay (An et al., 2017); This variant is associated with the following publications: (PMID: 27001614, 27460824, 30181556, 27390188) |