ClinVar Genomic variation as it relates to human health

The classification of this deletion is uncertain, per ACMGG interpretation standards (see References). It affects protein-coding elements (Section 1, 0 points) but doesn’t overlap any known dosage sensitive genes or regions (Section 2, 0 points). Nine protein-coding genes are affected by the deletion (Section 3, 0 points). A review of public databases (ClinVar, DECIPHER) and the medical literature shows several patients with similar deletion. Coppola et al. describe a 31-year-old female with an assumed de novo ring chromosome 17 who had moderate intellectual disability, absent speech, and drug-resistant epilepsy (epileptic encephalopathy) with an onset at age 4. Microarray showed no loss of genomic material from the short arm of chromosome 17 and a slightly smaller terminal deletion than seen in this patient (section 4C, 0.10 points). Probst et al. patient 4 was born with low birth weight, a tethered cord, a tracheoesophageal fistula, a cardiac VSD and PDA, and agenesis of the corpus callosum. She showed global developmental delay, distinctive facial features, mild contractures of her legs, and normal growth at age 12 years. She was found to have an assumed de novo 800 kb terminal deletion of chromosome 17q (section 4C, 0.10 points). DECIPHER patient 263357 is a 3 years 9 months with an abnormal facial shape and global developmental delay, found to have a 575 kb assumed de novo, isolated terminal deletion of 17q (section 4C, 0.10 points). DECIPHER and ClinVar contain 7 additional patients who have inherited a terminal deletion of 17q similar in size to the one seen here. The patients have a variety of clinical features, and no information is available about whether or not the carrier parent is healthy. The Database of Genomic Variants (DGV) includes one similar terminal deletion (nsv1067553, seen in 1 of 29,084 people). There are no similar deletions in gnomAD. Parental testing has not been done in this case (Section 5, 0 points).