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Limited information on phenotypes attributable to<jats:italic>RAD21<\/jats:italic>variants and genotype\u2013phenotype relationships is currently published. We gathered a series of 49 individuals from 33 families with<jats:italic>RAD21<\/jats:italic>alterations [24 different intragenic sequence variants (2 recurrent), 7 unique microdeletions], including 24 hitherto unpublished cases. We evaluated consequences of 12 intragenic variants by protein modelling and molecular dynamic studies. Full clinical information was available for 29 individuals. Their phenotype is an attenuated CdLS phenotype compared to that caused by variants in<jats:italic>NIPBL<\/jats:italic>or<jats:italic>SMC1A<\/jats:italic>for facial morphology, limb anomalies, and especially for cognition and behavior. In the 20 individuals with limited clinical information, additional phenotypes include Mungan syndrome (in patients with biallelic variants) and holoprosencephaly, with or without CdLS characteristics. We describe several additional cases with phenotypes including sclerocornea, in which involvement of the<jats:italic>RAD21<\/jats:italic>variant is uncertain. Variants were frequently familial, and genotype\u2013phenotype analyses demonstrated striking interfamilial and intrafamilial variability. Careful phenotyping is essential in interpreting consequences of<jats:italic>RAD21<\/jats:italic>variants, and protein modeling and dynamics can be helpful in determining pathogenicity. The current study should be helpful when counseling families with a<jats:italic>RAD21<\/jats:italic>variation.<\/jats:p>","DOI":"10.1007\/s00439-020-02138-2","type":"journal-article","created":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T12:04:24Z","timestamp":1584619464000},"page":"575-592","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Delineation of phenotypes and genotypes related to cohesin structural protein RAD21"],"prefix":"10.1007","volume":"139","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-2011","authenticated-orcid":false,"given":"Lianne 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