Submissions for variant NM_177924.5(ASAH1):c.290T>G (p.Val97Gly)

dbSNP: rs1588989964

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Medical Affairs, Dicerna Pharmaceuticals	RCV001003300	SCV001161383	likely pathogenic	Farber lipogranulomatosis	2019-06-18	criteria provided, single submitter	literature only	Variant c.290T>G has been given the clinical significance of likely pathogenic for the following reasons. Two siblings, girl and boy twins, were diagnosed with Farber disease characteristic of Type 5 Farber disease described in Gene Reviews (https://www.ncbi.nlm.nih.gov/books/NBK488189/). Both children were born from consanguineous parents and are homozygous for c.290T>G variants. The parents and a sibling sister are healthy carriers of the variant on a single allele. The mutation site was found to be highly conserved among different species using ClustalW2 alignment. Functional prediction tools indicated the mutation to be pathogenic. Electron microscopy based ultrastructural studies using skin biopsy showed inclusion of enlarged lysosomes and presence of the zebra bodies which are characteristic of Farber disease.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001003300	SCV005016607	likely pathogenic	Farber lipogranulomatosis	2024-03-14	criteria provided, single submitter	clinical testing