ClinVar Genomic variation as it relates to human health

This copy number loss includes the JARID2 gene (OMIM 601594), among others. Although JARID2 gene has not been associated with an OMIM phenotype, chromosomal deletions in 6p22-p24 involving JARID2 have been identified in multiple patients with common phenotypes including borderline intellectual functioning to severe intellectual disability (ID) and share characteristic facial features, including prominent supraor bital ridges, deep set eyes, infraorbital dark circles, and midface hypoplasia. JARID2 and DTNBP1 were the only 2 genes involved in a proposed critical region which was responsible for the majority of the phenotypes. A 6.5-year-old boy with a deletion involving only JARID2 and DTNBP1 genes was among the reported patients (Baroy et al. 2013). A recent multi-center study reported 16 individuals from 15 unrelated families, who had overlapping clinical features including developmental delay and/or ID and a deletion or sequencing variants in JARID2 gene (3 missense and 13 loss-of-function variants). Nine out of 13 loss-of-function variants, including 1 nonsense, 1 splicing, 2 frame shift, and 5 partial focal deletions, were confirmed de novo. In addition, biallelic pathogenic variants in this gene cause autosomal recessive Hermansky-Pudlak syndrome 7 (OMIM 614076). There are no similar copy number losses of this region in the general population of the Database of Genomic Variants (DGV). The evidence of haploinsufficiency of JARID2 gene is still emerging. Therefore, this copy number variant is classified as likely pathogenic. References: Baroy et al., Orphanet J Rare Dis. 2013 Jan 7;8:3. PMID: 23294540. Verberne et al., Genet Med. 2021 Feb;23(2):374-383. PMID: 33077894.