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To date, all pathogenic variants in <jats:italic>SMARCA2<\/jats:italic> causing NCBRS are <jats:italic>de novo<\/jats:italic> and most are missense variants located in the ATPase domain of SMARCA2 protein.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, a familial trio whole\u2010exome sequencing was performed on the proband presenting with intellectual disability, early\u2010onset epilepsy, and autistic features. A novel missense variant c.553C&gt;G (p.Gln185Glu) in <jats:italic>SMARCA2<\/jats:italic> was identified, which is located in the QLQ domain. The same variant was subsequently also found in the mother's ongoing pregnancy. Samples from accessible tissues such as saliva and sperm other than blood were collected from the parents, and the detection of the target variant was performed by amplicon\u2010based deep sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Low\u2010level mosaicism of the target variant c.553C&gt;G (p.Gln185Glu) was detected in the father's sperm with allele fraction of 2.8% by amplicon\u2010based deep sequencing, which was not detected in either parents\u2019 blood or saliva specimens. Heterozygosity of this variant was confirmed in the proband.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first report of paternal germline mosaicism for a <jats:italic>SMARCA2<\/jats:italic> disease\u2010causing variant. In addition, the missense variant c.553C&gt;G (p.Gln185Glu) in the QLQ domain causes mainly neurological and developmental phenotypes with unremarkable characteristic facial features and limb abnormalities. Our findings expand the phenotypic spectrum and mode of genetic transmission associated with the <jats:italic>SMARCA2<\/jats:italic> variants.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1763","type":"journal-article","created":{"date-parts":[[2021,7,23]],"date-time":"2021-07-23T06:28:12Z","timestamp":1627021692000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Low\u2010level germline mosaicism of a novel <i>SMARCA2<\/i> missense variant: Expanding the phenotypic spectrum and mode of genetic transmission"],"prefix":"10.1002","volume":"9","author":[{"given":"Nina","family":"Pan","sequence":"first","affiliation":[{"name":"International Peace Maternity and Child Health Hospital, School of Medicine Shanghai Jiao Tong University Shanghai China"},{"name":"Shanghai Key Laboratory of Embryo Original Diseases Shanghai 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