Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000022707 | SCV000816664 | likely pathogenic | Spondyloenchondrodysplasia with immune dysregulation | 2023-03-30 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Experimental studies have shown that this missense change affects ACP5 function (PMID: 27390188, 32214327). 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. ClinVar contains an entry for this variant (Variation ID: 29831). This missense change has been observed in individuals with clinical features of ACP5-related conditions and/or spondyloenchondrodysplasia (PMID: 21217752, 21217755, 27390188; Rosmaninho-Salgado J et al. 2015. SPGH November (19):69 P11). This variant is present in population databases (rs387906670, gnomAD 0.002%). This sequence change replaces methionine, which is neutral and non-polar, with lysine, which is basic and polar, at codon 264 of the ACP5 protein (p.Met264Lys). |
OMIM | RCV000022707 | SCV000043996 | pathogenic | Spondyloenchondrodysplasia with immune dysregulation | 2011-02-01 | no assertion criteria provided | literature only |