ClinVar Genomic variation as it relates to human health

This deletion interval fully overlaps the 15q25.2q25.3 recurrent region (LCR C-D, distal), which has been observed in individuals with developmental delay and intellectual disability. Case-control studies in children with developmental delay, intellectual disability, multiple congenital anomalies, and other developmental phenotypes showed that heterozygous deletions of this region were enriched in the clinical population (Coe et al., Nat Genet 2014;46(10):1063-71, PMID: 25217958). Additionally, in a large-scale case-control comparison study of copy number variants (CNV) in 15,767 children with developmental delay and intellectual disability, five patients were described with distal microdeletions of 15q25.2q25.3 similar or smaller than the current deletion. Three of these patients were described to have developmental delay (one also had a seizure disorder), one had autism, and one had hypotonia (Cooper et al., Nat Genet 2011 Aug 14;43(9):838-46, PMID: 21841781). Otherwise, heterozygous deletions of this locus have not yet been associated with an established clinical phenotype, and there are two similar copy number losses of this region in the general populations of the Database of Genomic Variants. Thus, conservatively, the clinical significance of this recurrent region is regarded as likely pathogenic.