Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000694951 | SCV000823421 | pathogenic | Spondyloenchondrodysplasia with immune dysregulation | 2023-11-11 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 215 of the ACP5 protein (p.Gly215Arg). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with spondyloenchondrodysplasia and isolated autoimmune cytopenias (PMID: 21217752, 21217755, 26951490, 27718324). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 573309). 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 with a negative predictive value of 80%. Experimental studies have shown that this missense change affects ACP5 function (PMID: 32214327). For these reasons, this variant has been classified as Pathogenic. |
Ce |
RCV002510960 | SCV002822513 | likely pathogenic | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | ACP5: PM2, PM3, PP3, PP4, PS3:Supporting |