current Homo sapiens Xp22.2 300170 Sufficient evidence for dosage pathogenicity No evidence available NM_003611.2(OFD1):c.936-550_936-537delACACTTGGGCTCAA Deletion Xp22.2 NC_000023.11:g.13750699_13750712delACACTTGGGCTCAA NC_000023.10:g.13768818_13768831delACACTTGGGCTCAA NM_003611.2:c.936-550_936-537delACACTTGGGCTCAA NG_008872.1:g.20987_21000delACACTTGGGCTCAA Xp22.2 300170 Sufficient evidence for dosage pathogenicity No evidence available NG_008872.1:g.16740_20819del4080 Deletion Xp22.2 NC_000023.11:g.13746452_13750531del NC_000023.10:g.13764571_13768650del NG_008872.1:g.16740_20819del NCBI staff reviewed the sequence in the paper by Morisawa et al., PubMed 15221448 to represent the breakpoints. The right-most possible location in the region of ambiguity was selected. NG_008872.1(OFD1):g.[16740_20819del;g.20987_21000del] Haplotype NG_008872.1:g.[16740_20819del;g.20987_21000del] no assertion criteria provided Oral-facial-digital syndrome Pathogenic 15221448 Pathogenic/Likely pathogenic Pathogenic OFDS I Papillon-Leage and Psaume Syndrome Oral-facial-digital syndrome Oral-Facial-Digital Syndrome Type I OFD1 CXORF5 Hereditary cancer syndrome Oral-facial-digital syndrome type I (OFD1) is usually male lethal during gestation and predominantly affects females. OFD1 is characterized by the following features: Oral (lobulated tongue, tongue nodules, cleft of the hard or soft palate, accessory gingival frenulae, hypodontia, and other dental abnormalities). Facial (widely spaced eyes or telecanthus, hypoplasia of the alae nasi, median cleft or pseudocleft upper lip, micrognathia). Digital (brachydactyly, syndactyly, clinodactyly of the fifth finger; duplicated hallux [great toe]). Kidney (polycystic kidney disease). Brain (e.g., intracerebral cysts, agenesis of the corpus callosum, cerebellar agenesis with or without Dandy-Walker malformation). Intellectual disability (in ~50% of individuals). 20301367 NBK1188 current no assertion criteria provided Pathogenic variation to disease germline human not provided literature only In a Japanese woman with sporadic OFD I (311200), Morisawa et al. (2004) identified a pair of deletions in the CXORF5 gene: a 4,094-bp deletion encompassing exon 7 to intron 9, and a 14-bp deletion in intron 9, both of which were present in her paternal X chromosome. The first deletion, the largest identified in the CXORF5 gene to that time, was revealed by identifying 4 novel transcripts that all lacked exons 7-9. The most likely cause of the double deletion was considered to be 2 unequal recombinations between homologous sequences. Identification of the 4,094-bp deletion was made possible only by analyzing CXORF5 mRNA, underscoring the utility of mRNA study in the mutation analysis of the CXORF5 gene. 15221448 OFD1, 4,094-BP DEL, 14-BP DEL Variation 4,094-BP DEL, 14-BP DEL OROFACIODIGITAL SYNDROME I current Homo sapiens 2q32.2 120180 Sufficient evidence for dosage pathogenicity No evidence available gene_acmg_incidental_2013 NM_000090.3(COL3A1):c.[=/3440_3466del27] (p.Pro1147_Gly1155del) Deletion NM_000090.3:c.[=/3440_3466del27] NP_000081.1:p.Pro1147_Gly1155del LRG_3t1:c.[=/3440_3466del27] LRG_3p1:p.Pro1147_Gly1155del Mosaic for two separate 27bp deletions in exon 48 in two cell strains of equal proportion current Homo sapiens 2q32.2 120180 Sufficient evidence for dosage pathogenicity No evidence available gene_acmg_incidental_2013 NM_000090.3(COL3A1):c.[=/3426_3452del27] (p.Gly1143_Asp1151del) Deletion NM_000090.3:c.[=/3426_3452del27] NP_000081.1:p.Gly1143_Asp1151del LRG_3t1:c.[=/3426_3452del27] LRG_3p1:p.Gly1143_Asp1151del Mosaic for two separate 27bp deletions in exon 48 in two cell strains of equal proportion current Homo sapiens 2q32.2 120180 Sufficient evidence for dosage pathogenicity No evidence available gene_acmg_incidental_2013 NM_000090.3(COL3A1):c.3851G>A (p.Gly1284Glu) single nucleotide variant 2q32.2 G1284E NC_000002.12:g.189010205G>A NC_000002.11:g.189874931G>A LRG_3t1:c.3851G>A LRG_3p1:p.Gly1284Glu NM_000090.3:c.3851G>A NP_000081.1:p.Gly1284Glu NG_007404.1:g.40833G>A LRG_3:g.40833G>A two mutations on different alleles based on family studies current Homo sapiens 3p22.2 120436 Sufficient evidence for dosage pathogenicity No evidence available gene_acmg_incidental_2013 NM_000249.3(MLH1):c.545+1271_677+737delinsCA Indel 3p22.2 NC_000003.11:g.37051667_37054327del2661insCA NC_000003.12:g.37010176_37012836del2661insCA LRG_216t1:c.545+1271_677+737delinsCA NM_000249.3:c.545+1271_677+737delinsCA current Homo sapiens 3p22.2 120436 Sufficient evidence for dosage pathogenicity No evidence available gene_acmg_incidental_2013 NM_000249.3(MLH1):c.453+625_545+921delinsTG Indel 3p22.2 NM_000249.3:c.453+625_545+921delinsTG NC_000003.12:g.37007688_37009826del2139insTG NC_000003.11:g.37049179_37051317del2139insTG LRG_216t1:c.453+625_545+921delinsTG current Homo sapiens 16p13.3 191092 Sufficient evidence for dosage pathogenicity No evidence available gene_acmg_incidental_2013 NM_000548.4(TSC2):c.4361_4372delGTGGCCTCCGGC (p.Ser1454_Pro1458delinsThr) Deletion 16p13.3 NC_000016.9:g.2134584_2134595delGTGGCCTCCGGC NC_000016.10:g.2084583_2084594delGTGGCCTCCGGC NM_000548.4:c.4361_4372delGTGGCCTCCGGC NP_000539.2:p.Ser1454_Pro1458delinsThr NM_000548.3:c.4361_4372del12 NP_000539.2:p.Ser1454_Pro1458delinsThr LRG_487t1:c.4361_4372delGTGGCCTCCGGC LRG_487p1:p.Ser1454_Pro1458delinsThr LRG_487:g.40278_40289delGTGGCCTCCGGC NG_005895.1:g.40278_40289delGTGGCCTCCGGC current Homo sapiens 16p13.3 191092 Sufficient evidence for dosage pathogenicity No evidence available gene_acmg_incidental_2013 NM_000548.4(TSC2):c.4358_4359delCC (p.Pro1453Glnfs) Deletion 16p13.3 NM_000548.4:c.4358_4359delCC NP_000539.2:p.Pro1453Glnfs LRG_487:g.40275_40276delCC NG_005895.1:g.40275_40276delCC NC_000016.9:g.2134581_2134582delCC NC_000016.10:g.2084580_2084581delCC LRG_487t1:c.4358_4359delCC LRG_487p1:p.Pro1453Glnfs current Homo sapiens 6q24.2 612243 NM_198569.2(ADGRG6):c.2306T>A (p.Val769Glu) single nucleotide variant 6q24.2 V769E NC_000006.11:g.142729324T>A NC_000006.12:g.142408187T>A NM_198569.2:c.2306T>A NP_940971.1:p.Val769Glu NM_020455.5:c.2306T>A NP_065188.4:p.Val769Glu NG_011839.1:g.111269T>A Pathogenic 26004201 Arthrogryposis multiplex congenita AMC Arthrogryposis multiplex congenita (AMC) is a heterogeneous group of disorders characterized by congenital nonprogressive joint contractures, with a worldwide incidence of 1 in 3,000 live births. AMC can occur in the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth (summary by Markus et al., 2012). There is also a distal form of arthrogryposis multiplex congenita (see DA1A, 108120) and a lethal congenital form (see LCCS1, 253310). 6q24.2 612243 NM_020455.5(ADGRG6):c.2222T>A (p.Val741Asp) single nucleotide variant 6q24.2 V741D V741E NC_000006.11:g.142726919T>A NC_000006.12:g.142405782T>A NM_020455.5:c.2222T>A NP_065188.4:p.Val741Asp NG_011839.1:g.108864T>A Pathogenic 26004201 Lethal congenital contracture syndrome 9 LCCS9 NM_198569.2(ADGRG6):c.[2222T>A;2306T>A] Haplotype NM_198569.2:c.[2222T>A;2306T>A] Pathogenic current Homo sapiens 19q13.32 107741 NM_000041.3(APOE):c.388T>C (p.Cys130Arg) single nucleotide variant 19q13.32