{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T07:12:33Z","timestamp":1787987553557,"version":"build-2784847793"},"reference-count":24,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,8,31]],"date-time":"2023-08-31T00:00:00Z","timestamp":1693440000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt C"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Heterozygous <jats:italic>ARID1B<\/jats:italic> variants result in Coffin\u2013Siris syndrome. Features may include hypoplastic nails, slow growth, characteristic facial features, hypotonia, hypertrichosis, and sparse scalp hair. Most reported cases are due to <jats:italic>ARID1B<\/jats:italic> loss of function variants. We report a boy with developmental delay, feeding difficulties, aspiration, recurrent respiratory infections, slow growth, and hypotonia without a clinical diagnosis, where a previously unreported <jats:italic>ARID1B<\/jats:italic> missense variant was classified as a variant of uncertain significance. The pathogenicity of this variant was refined through combined methodologies including genome\u2010wide methylation signature analysis (EpiSign), Machine Learning (ML) facial phenotyping, and LIRICAL. Trio exome sequencing and EpiSign were performed. ML facial phenotyping compared facial images using FaceMatch and GestaltMatcher to syndrome\u2010specific libraries to prioritize the trio exome bioinformatic pipeline gene list output. Phenotype\u2010driven variant prioritization was performed with LIRICAL. A de novo heterozygous missense variant, <jats:italic>ARID1B<\/jats:italic> p.(Tyr1268His), was reported as a variant of uncertain significance. The ACMG classification was refined to likely pathogenic by a supportive methylation signature, ML facial phenotyping, and prioritization through LIRICAL. The <jats:italic>ARID1B<\/jats:italic> genotype\u2013phenotype has been expanded through an extended analysis of missense variation through genome\u2010wide methylation signatures, ML facial phenotyping, and likelihood\u2010ratio gene prioritization.<\/jats:p>","DOI":"10.1002\/ajmg.c.32056","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T06:31:52Z","timestamp":1693549912000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Integration of <scp>EpiSign<\/scp>, facial phenotyping, and likelihood ratio interpretation of clinical abnormalities in the re\u2010classification of an <scp><i>ARID1B<\/i><\/scp> missense variant"],"prefix":"10.1002","volume":"193","author":[{"given":"Caitlin","family":"Forwood","sequence":"first","affiliation":[{"name":"NSW Health Pathology Randwick Genomics Prince of Wales Hospital  Sydney Australia"},{"name":"Centre for Clinical Genetics Sydney Children's 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Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystle","family":"Standen","sequence":"additional","affiliation":[{"name":"NSW Health Pathology Randwick Genomics Prince of Wales Hospital  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carey\u2010Anne","family":"Evans","sequence":"additional","affiliation":[{"name":"Neuroscience Research Australia (NeuRA) University of New South Wales  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Carey","sequence":"additional","affiliation":[{"name":"NSW Health Pathology Randwick Genomics Prince of Wales Hospital  Sydney Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Cardamone","sequence":"additional","affiliation":[{"name":"Sydney Children's Hospital  Randwick Australia"},{"name":"School of Women's and Children's Health UNSW  Sydney 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