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Additionally, the cohesin complex regulates DNA replication, DNA repair, and transcription. The core of the complex consists of four subunits: SMC1A, SMC3, RAD21, and STAG1\/2. Loss\u2010of\u2010function mutations in many of these proteins have been implicated in human developmental disorders collectively termed \u201ccohesinopathies.\u201d Through clinical exome sequencing (CES) of an 8\u2010year\u2010old girl with a clinical history of global developmental delay, microcephaly, microtia with hearing loss, language delay, ADHD, and dysmorphic features, we describe a heterozygous de novo variant (c.205C&gt;T; p.(Arg69*)) in the integral cohesin structural protein, <jats:italic>STAG2<\/jats:italic>. This variant is associated with decreased STAG2 protein expression. The analyses of metaphase spreads did not exhibit premature sister chromatid separation; however, delayed sister chromatid cohesion was observed. To further support the pathogenicity of <jats:italic>STAG2<\/jats:italic> variants, we identified two additional female cases from the DECIPHER research database with mutations in <jats:italic>STAG2<\/jats:italic> and phenotypes similar to our patient. Interestingly, the clinical features of these three cases are remarkably similar to those observed in other well\u2010established cohesinopathies. Herein, we suggest that <jats:italic>STAG2<\/jats:italic> is a dosage\u2010sensitive gene and that heterozygous loss\u2010of\u2010function variants lead to a cohesinopathy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38207","type":"journal-article","created":{"date-parts":[[2017,3,11]],"date-time":"2017-03-11T12:32:56Z","timestamp":1489235576000},"page":"1319-1327","source":"Crossref","is-referenced-by-count":58,"title":["De novo loss\u2010of\u2010function variants in <i>STAG2<\/i> are associated with developmental delay, microcephaly, and congenital anomalies"],"prefix":"10.1002","volume":"173","author":[{"given":"Sureni V.","family":"Mullegama","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine David Geffen School of Medicine University of California Los Angeles California"},{"name":"UCLA Clinical Genomics Center, David Geffen School of Medicine University of California Los Angeles 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