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Combined autozygome\/exome analysis was performed in two unrelated consanguineous families with ID. Each of the two families had a novel homozygous likely deleterious variant in <jats:italic>PLXNA2<\/jats:italic> and displayed the core phenotype of ID. <jats:italic>PLXNA2<\/jats:italic> belongs to a family of transmembrane proteins that function as semaphorin receptors. Sema5A\u2010PlexinA2 is known to regulate brain development in mouse, and <jats:italic>Plxna2<\/jats:italic>\u2212\/\u2212 mice display defective associative learning, sociability, and sensorimotor gating. We note the existence of variability in the phenotype among the three patients, including the existence of variable degree of ID, ranging from borderline intellectual functioning to moderate\u2013severe ID, and the presence of cardiac anomalies in only one of the patients. We propose incomplete penetrance as a possible explanation of the observed difference in phenotypes. Future cases will be needed to support the proposed link between <jats:italic>PLXNA2<\/jats:italic> and ID in humans.<\/jats:p>","DOI":"10.1002\/ajmg.a.62440","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T06:02:24Z","timestamp":1627624944000},"page":"3859-3865","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["<scp><i>PLXNA2<\/i><\/scp> as a candidate gene in patients with intellectual disability"],"prefix":"10.1002","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4363-0753","authenticated-orcid":false,"given":"Fadie D.","family":"Altuame","sequence":"first","affiliation":[{"name":"College of Medicine Alfaisal University  Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanan E.","family":"Shamseldin","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, Center for Genomic Medicine King 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