ClinVar Genomic variation as it relates to human health

This CNV is a 5.1 Mb deletion of 13q12.3-q13.2, on chromosome 13, (seq[GRCh37]del(13)( 13q12.3q13.2); chr13:g.28925153_34061696del) of unknown inheritance. This CNV constitutes a loss encompassing 45 genes. At least four de novo deletions in the 13q12.3 region have been identified in individuals presenting with developmental delay, intellectual disability, language impairment, atopic dermatitis, hyperactivity, and variable dysmorphic features including malar flattening, prominent nose with underdeveloped alae nasi, smooth philtrum, and thin vermillion of the upper lip. Additional features in these individuals included hearing loss, camptodactyly, hypothyroidism, hip dysplasia, congenital hernia of diaphragm, cryptorchidism, and abnormal brain MRI (Bartholdi et al. 2014; D'Angelo et al. 2018). The proximal and distal breakpoints of the CNVs were clustered and the deletions spanned in size from 1.4 to 4.4 Mb. A 300 kb region harboring three genes, namely, KATNAL1, HMGB1, and the non-protein coding RNA LINC00426 has been implicated as the critical region (Mandrile et al. 2014). Additionally, there are several patients with deletions in this region in the DECIPHER database who are noted to display overlapping phenotypic features, including intellectual disability, language delay, microcephaly, and facial dysmorphisms. In particular, one overlapping loss of similar size (5.2 Mb) was reported in an individual with hypertelorism, intellectual disability, short stature, abnormal vertebral morphology, pectus excavatum, webbed neck, and constipation (Firth et al. 2009). This CNV has not been reported in controls. Based on the collective evidence, this CNV is classified as pathogenic.