ClinVar Miner

Submissions for variant NM_177924.5(ASAH1):c.502G>T (p.Gly168Trp)

dbSNP: rs1421841663
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Medical Affairs, Dicerna Pharmaceuticals RCV001003306 SCV001161390 pathogenic Farber lipogranulomatosis 2019-06-19 criteria provided, single submitter literature only Variant c.502G>T has been classified as pathogenic. The patient described in Cvitanovic-Sojat et al., 2011, doi:10.1016/j.ejpn.2010.06.002, was diagnosed with Type 1 Farber disease symptoms described in Gene Reviews ( Microscopic examination of subcutaneous and periarticular tissues showed the accumulation of macrophages, histiocytes, foam cells and PAS-positive material which is indicative of Farber disease. Homozygous c.502G>T variants were discovered through whole genome sequencing and confirmed at the cDNA level. A ceramide loading test was carried out using intact cultured skin fibroblasts. In the patient's cells, undegraded lysosomal ceramide represented 56% of radioactive sphingomyelin metabolites, compared to 2-7.5% in control cells. Acid ceramidase deficiency was confirmed using an in vitro assay measuring enzyme activity in fibroblast lysates. The patient's ceramidase activity was found to be undetectable [normal range 0.011-0.084 nmol/h/mg protein (n=9); mean 0.047]. Other lysosomal enzymes were within the normal range.

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