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Here, we describe an infant with severe, diffuse hypotonia, congenital contractures, and pulmonary hypoplasia characteristic of SMABF2, with the unique features of cleft palate, small spleen, transverse liver, and pulmonary thromboemboli with chondroid appearance. This infant also had impaired coagulation with diffuse petechiae and ecchymoses which has only been reported in one other infant with AMC. Using trio whole genome sequencing, our proband was identified to have biallelic variants in <jats:italic>ASCC1<\/jats:italic>. Using deep next generation sequencing of parental cDNA, we characterized alteration of splicing encoded by the novel, maternally inherited <jats:italic>ASCC1<\/jats:italic> variant (c.297\u20108\u00a0T\u2009&gt;\u2009G) which provides a mechanism for functional pathogenicity. The paternally inherited <jats:italic>ASCC1<\/jats:italic> variant is a rare nonsense variant (c.466C\u2009&gt;\u2009T; p.Arg156*) that has been previously identified in one other infant with AMC. This report extends the phenotypic characteristics of <jats:italic>ASCC1<\/jats:italic>\u2010associated AMC (SMABF2) and describes a novel intronic variant that partially disrupts RNA splicing.<\/jats:p>","DOI":"10.1002\/ajmg.a.62219","type":"journal-article","created":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T07:24:34Z","timestamp":1619853874000},"page":"2190-2197","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Biallelic <scp><i>ASCC1<\/i><\/scp> variants including a novel intronic variant result in expanded phenotypic spectrum of spinal muscular atrophy with congenital bone fractures 2 (<scp>SMABF2<\/scp>)"],"prefix":"10.1002","volume":"185","author":[{"given":"Kristen K.","family":"Rosano","sequence":"first","affiliation":[{"name":"Division of Newborn Medicine, Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Wegner","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwan","family":"Shinawi","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomic Medicine Department of Pediatrics, Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6027-6020","authenticated-orcid":false,"given":"Dustin","family":"Baldridge","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomic Medicine Department of Pediatrics, Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Bucelli","sequence":"additional","affiliation":[{"name":"Department of Neurology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonika","family":"Dahiya","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances V.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia C.","family":"Willing","sequence":"additional","affiliation":[{"name":"Division of Genetics and Genomic Medicine Department of Pediatrics, Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"McAllister","sequence":"additional","affiliation":[{"name":"Mallinckrodt Institute of Radiology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan J.","family":"Taft","sequence":"additional","affiliation":[{"name":"Illumina, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krista","family":"Bluske","sequence":"additional","affiliation":[{"name":"Illumina, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Buchanan","sequence":"additional","affiliation":[{"name":"Illumina, Inc.  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis Sessions","family":"Cole","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9299-0499","authenticated-orcid":false,"given":"Jennifer A.","family":"Wambach","sequence":"additional","affiliation":[{"name":"Division of Newborn Medicine, Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.2106\/JBJS.I.00281"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105390"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddw033"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2431-13-59"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61431"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2014.03.008"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.14.5203-5211.2002"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2016.01.006"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1212"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00131402-199912000-00002"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12997"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62219","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.62219","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.62219","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T08:44:00Z","timestamp":1692953040000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.62219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5]]},"references-count":12,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["10.1002\/ajmg.a.62219"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.62219","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5]]},"assertion":[{"value":"2020-12-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-03-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}