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It has been recognized as the most common cause underlying primary MDS in children. Triggered by the discovery of a recurrent synonymous <jats:italic>GATA2<\/jats:italic> variant, we systematically investigated 911 patients with phenotype of pediatric MDS or cellular deficiencies for the presence of synonymous alterations in <jats:italic>GATA2<\/jats:italic>. In total, we identified nine individuals with five heterozygous synonymous mutations: c.351C&gt;G,\u00a0p.T117T (<jats:italic>N<\/jats:italic>\u2009=\u20094); c.649C&gt;T,\u00a0p.L217L; c.981G&gt;A,\u00a0p.G327G; c.1023C&gt;T,\u00a0p.A341A; and c.1416G&gt;A,\u00a0p.P472P (<jats:italic>N<\/jats:italic>\u2009=\u20092). They accounted for 8.2% (9\/110) of cases with GATA2 deficiency in our cohort and resulted in selective loss of mutant RNA. While for the hotspot mutation (c.351C&gt;G) a splicing error leading to RNA and protein reduction was identified, severe, likely late stage RNA loss without splicing disruption was found for other mutations. Finally, the synonymous mutations did not alter protein function or stability. In summary, synonymous <jats:italic>GATA2<\/jats:italic> substitutions are a new common cause of GATA2 deficiency. These findings have broad implications for genetic counseling and pathogenic variant discovery in Mendelian disorders.<\/jats:p>","DOI":"10.1038\/s41375-020-0899-5","type":"journal-article","created":{"date-parts":[[2020,6,18]],"date-time":"2020-06-18T10:04:33Z","timestamp":1592474673000},"page":"2673-2687","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Synonymous GATA2 mutations result in selective loss of mutated RNA and are common in patients with GATA2 deficiency"],"prefix":"10.1038","volume":"34","author":[{"given":"Emilia J.","family":"Kozyra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor 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