TABLE 1.
Novel variants in genes previously described in association with non-syndromic cleft palate only (NSCPO) found exclusively in the samples of patients with NSCPO.
| Gene | Protein | Variants | Chr:Pos | MAF 1K | MAF gnomAD Exomes | MAF gnomAD Genomes | MAF ExAC | MAF ABraOM | Sequence Ontology | SIFT | Polyphen2 | Mutation Taster | OMIM Number | References |
| ACACB | Acetyl-CoA Carboxylase Beta | rs60293430 | 12:109665242 | 0.0517173 | 0.0479439 | 0.0660566 | 0.049 | 0.066183 | missense | Tolerated | Possibly damaging | Damaging | *601557 | Hoebel et al., 2017 |
| CDH1† | Cadherin 1 | rs33969373 | 16:68856088 | 0.0227636 | 0.0103762 | 0.0177832 | 0.011 | 0.038588 | synonymous | - | - | - | *192090 | Song and Zhang, 2011 |
| rs33964119 | 16:68862165 | 0.0545128 | 0.0426288 | 0.0346343 | 0.04 | 0.037767 | synonymous | - | - | - | ||||
| COL2A1* | Collagen Type II Alpha 1 Chain | rs34392760 | 12:48391657 | 0.0179712 | 0.0376268 | 0.0349919 | 0.038 | 0.047619 | missense | Tolerated | Benign | Damaging | +120140 | Li et al., 1995; Nikopensius et al., 2010 |
| COL11A1* | Collagen Type XI Alpha 1 Chain | rs1012281 | 1:103427407 | 0.038139 | 0.0516874 | 0.0579359 | 0.053 | 0.068144 | intron | - | - | - | *120280 | Seegmiller et al., 1971 |
| rs771593293 | 1:103468856 | - | - | - | - | 0.087800 | - | - | - | - | ||||
| rs111841420 | 1:103470191 | 0.0183706 | 0.0245013 | 0.022501 | 0.023 | 0.025452 | synonymous | - | - | - | ||||
| rs3767272 | 1:103483329 | 0.0347444 | 0.0296967 | 0.0200607 | 0.03 | 0.026273 | intron | - | - | - | ||||
| COL11A2* | Collagen Type XI Alpha 2 Chain | rs2229784 | 6:33136310 | 0.057508 | 0.0344903 | 0.0395325 | 0.034 | 0.051724 | missense | Damaging | Possibly damaging | Damaging | *120290 | Nikopensius et al., 2010 |
| rs73741526 | 6:33139635 | 0.0810703 | 0.0464905 | 0.0476175 | 0.047 | 0.064860 | intron | - | - | - | ||||
| rs2855430 | 6:33141280 | 0.102236 | 0.121898 | 0.106553 | 0.122 | 0.084565 | missense | Tolerated | Probably damaging | Damaging | ||||
| rs9280359 | 6:33142013 | 0.202476 | 0.162732 | 0.189819 | 0.1 | 0.178053 | intron | - | - | - | ||||
| rs41317098 | 6:33144466 | 0.102436 | 0.0473386 | 0.115006 | 0.052 | 0.077997 | intron | - | - | - | ||||
| rs2744507 | 6:33148878 | 0.102636 | 0.121967 | 0.106294 | 0.122 | 0.085386 | intron | - | - | - | ||||
| CREBBP* | CREB Binding Protein | rs73491901 | 16:3781845 | 0.00139776 | 0.0003691 | 0.0021309 | 0.0004942 | 0.001281 | missense | Tolerated | Possibly damaging | Damaging | *600140 | Hoebel et al., 2017 |
| rs130004 | 16:3828207 | 0.0553115 | 0.0137934 | 0.0517921 | 0.017 | 0.027754 | intron | - | - | - | ||||
| rs130018 | 16:3831187 | 0.0780751 | 0.0281749 | 0.069947 | 0.033 | 0.052519 | intron | - | - | - | ||||
| FTCD† | Formimidoyltransferase Cyclodeaminase | rs10432965 | 21:47557222 | 0.167532 | 0.0830084 | 0.0992947 | 0.087 | 0.091954 | synonymous | Damaging | Benign | Damaging | *606806 | Boyles et al., 2009 |
| GRHL3*,† | Grainyhead Like Transcription Factor 3 | rs34637004 | 1:24663184 | 0.0175719 | 0.0343092 | 0.0398771 | 0.033 | 0.033662 | missense | Tolerated | Benign | Tolerated | *608317 | Peyrard-Janvid et al., 2014; Leslie et al., 2016; Basha et al., 2018 |
| JAG2† | Jagged Canonical Notch Ligand 2 | rs78862296 | 14:105634205 | 0.00519169 | 0.00102047 | 0.0052073 | 0.001451 | 0.002467 | synonymous | - | - | - | *602570 | Jiang et al., 1998; Vieira et al., 2005; Jagomagi et al., 2010 |
| rs113906438 | 14:105613039 | 0.023762 | 0.0125495 | 0.0139761 | 0.011 | 0.018883 | synonymous | - | - | - | ||||
| LRP6*,† | LDL Receptor Related Protein 6 | rs34815107 | 12:12279735 | 0.00299521 | 0.00103964 | 0.0041338 | 0.001285 | 0.002463 | missense | Tolerated | Bening | Damaging | *603507 | Basha et al., 2018 |
| MSX1† | Msh Homeobox 1 | rs33929633 | 4:4864405 | 0.189696 | 0.216977 | 0.234219 | 0.215 | 0.206076 | intron | - | - | - | *142983 | Satokata and Maas, 1994; Jagomagi et al., 2010 |
| MTHFD1† | Methylenetetrahydrofolate Dehydrogenase, Cyclohydrolase And Formyltetrahydrofolate Synthetase 1 | rs60806768 | 14:64898459 | 0.0593051 | 0.0315681 | 0.0640463 | 0.036 | 0.047619 | intron | - | - | - | *172460 | Boyles et al., 2008; Murthy et al., 2014 |
| rs59770063 | 14:64898463 | 0.0593051 | 0.0315598 | 0.0639411 | 0.036 | 0.047619 | intron | - | - | - | ||||
| MTHFR† | Methylenetetrahydrofolate Reductase | rs45496998 | 1:11852412 | - | - | - | - | 0.002463 | - | - | - | - | *607093 | Shaw et al., 1999 |
| rs2274976 | 1:11850927 | 0.0744808 | 0.055472 | 0.0408481 | 0.056 | 0.033662 | missense | Tolerated | Benign | Tolerated | ||||
| MTR† | 5-Methyltetrahydrofolate-Homocysteine Methyltransferase | rs113277607 | 1:236971983 | 0.0421326 | 0.0113392 | 0.0400116 | 0.015 | 0.032020 | intron | - | - | - | *156570 | Boyles et al., 2008 |
| rs7526063 | 1:236971998 | 0.0744808 | 0.0374526 | 0.051899 | 0.04 | 0.049261 | splice region | - | - | - | ||||
| rs12022937 | 1:237060850 | 0.215056 | 0.0764726 | 0.146143 | 0.085 | 0.113300 | splice region | - | - | - | ||||
| OFD1* | OFD1 Centriole And Centriolar Satellite Protein | rs5979959 | X:13769452 | 0.00503311 | 0.00163061 | 0.00527241 | 0.001738 | 0.002994 | synonymous | - | - | - | *300170 | Ferrante et al., 2006; Jugessur et al., 2012 |
| rs140369491 | X:13779341 | 0.0362914 | 0.0130494 | 0.0185598 | 0.015 | 0.022954 | intron | - | - | - | ||||
| POMGNT2* | Protein O-Linked Mannose N-Acetylglucosaminyl transferase 2 (Beta 1,4-) | rs115870061 | 3:43122162 | 0.00499201 | 0.00106109 | 0.00432956 | 0.001491 | 0.00243 | synonymous | - | - | - | *614828 | Huang et al., 2019 |
| RFC1† | Replication Factor C Subunit 1 | rs2066782 | 4:39303925 | 0.106829 | 0.115582 | 0.0985123 | 0.115 | 0.096880 | synonymous | - | - | - | *600424 | Shaw et al., 2003; Boyles et al., 2008, 2009 |
| SHMT1 | Serine Hydroxymethyltransferase 1 | rs8080285 | 17:18234028 | 0.0924521 | 0.026609 | 0.0748126 | 0.031 | 0.068966 | intron | - | - | - | *182144 | Boyles et al., 2009 |
| rs2273026 | 17:18256979 | 0.135184 | 0.122439 | 0.109661 | 0.119 | 0.103448 | splice region | - | - | - | ||||
| SOX9* | SRY-Box Transcription Factor 9 | rs2229989 | 17:70118935 | 0.136581 | 0.193679 | 0.172156 | 0.192 | 0.157635 | synonymous | - | - | - | *608160 | Bi et al., 2001 |
| TBX1* | T-Box Transcription Factor 1 | rs139776757 | 22:19750797 | 0.000998403 | 0.0028023 | 0.0040708 | 0.003031 | 0.003284 | synonymous | - | - | - | *602054 | Basha et al., 2018 |
| TBX22* | T-Box Transcription Factor 22 | rs195293 | X:79283509 | 0.101457 | 0.0254122 | 0.0901992 | 0.029 | 0.092814 | synonymous | - | - | - | *300307 | Pauws et al., 2009 |
| TCN2† | Transcobalamin 2 | rs2283873 | 22:31013296 | 0.167133 | 0.0871466 | 0.1164 | 0.087 | 0.100985 | intron | - | - | - | *613441 | Martinelli et al., 2006 |
| rs9621049 | 22:31013419 | 0.108626 | 0.114338 | 0.127767 | 0.112 | 0.148604 | missense | Tolerated | Benign | Tolerated | ||||
| TCOF1* | Treacle Ribosome Biogenesis Factor 1 | rs73270831 | 5:149740772 | 0.00958466 | 0.00245265 | 0.00910853 | 0.003006 | 0.008210 | synonymous | - | - | - | *606847 | Dixon et al., 2000; Machado et al., 2016 |
| rs73270846 | 5:149756088 | 0.0091853 | 0.00238518 | 0.00898746 | 0.0029 | 0.008210 | missense | Tolerated | Possibly damaging | Tolerated | ||||
| rs2071240 | 5:149755744 | 0.0605032 | 0.0693377 | 0.0643264 | 0.069 | 0.045977 | missense | Damaging | Probably damaging | Tolerated | ||||
| rs11743855 | 5:149772932 | 0.0623003 | 0.0638 | 0.0878194 | 0.065 | 0.086207 | splice region | - | - | - | ||||
| TP63* | Tumor Protein P63 | rs33979049 | 3:189584563 | 0.0145767 | 0.0164723 | 0.0142811 | 0.017 | 0.012315 | synonymous | - | - | - | *603273 | Basha et al., 2018 |
| TYMS† | Thymidylate Synthetase | rs28602966 | 18:658170 | 0.0181709 | 0.027113 | 0.0262783 | 0.022 | 0.024752 | stop gained | - | - | - | *188350 | Boyles et al., 2009; Shaw et al., 2013 |
*Genes described in syndromes with cleft palate. †Genes described in cleft lip and palate. OMIM, Online Mendelian Inheritance in Man (http://omim.org). An asterisk (*) before an OMIM entry number indicates a gene. A plus sign (+) before an OMIM entry number indicates that the entry includes a description of a gene and a phenotype.