ClinVar Genomic variation as it relates to human health

This CNV is a 1.7 Mb deletion of 3q29, on chromosome 3, (seq[GRCh37]del(3)(q29);chr3:g.194498718_196196789del) which is inherited. This CNV constitutes a loss encompassing more than 50 genes, of which 15 are protein-coding with unclear information on haploinsufficiency. This CNV overlaps the proximal 400 kb region of a recurrent 1.6 Mb deletion associated with 3q29 microdeletion syndrome, which has been reported in more than 50 cases (Mulle et al. 2017). The 3q29 microdeletion syndrome is inherited in an autosomal dominant pattern, in most cases occurring de novo although at least eight cases have inherited a deletion from a mildly affected parent (Khan et al. 2019). The expressivity of 3q29 microdeletion syndrome is variable with common features including mild to moderate intellectual disability and language-based learning difficulties, speech delay, behavioral abnormalities consistent with autism and attention deficit disorder, and craniofacial dysmorphic features. Additional features in some individuals include chest deformities such as pectus carinatum, ocular abnormalities, joint contractures, heart defects, and gastrointestinal disorders (Cox et al. 2015; Glassford et al. 2016, Mulle et al. 2016). This CNV also partially overlaps a 1.2 Mb deletion reported in a male with microcephaly, dysmorphic facial features, cognitive delay, behavioral problems including ADHD, chest deformity, and scoliosis (Chirita Emandi et al. 2019). This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as a variant of uncertain significance.