Pathogenicity classifications for all identified variants in known primary ciliary dyskinesia (PCD) genes
| Study ID | Gene | RefSeq transcript | Variant (all homozygous) | Genomic location (GRCh38) | Exon/total | LOF | NMD (DECIPHER) | ACMG/AMP evidence | ACMG/AMP classification | ClinVar classification | Recorded in previous publications/similar population |
| 0-1, 0-2, 0-8, 0-9, 0-11, 0-20, 0-21, 0-25, 0-31 | CCDC39 | NM_181426.1 | c.1871_1872del; p.(Ile624Lysfs*3) | 3: 180641995_180641996del | 13/20 | Yes | Yes | PVS1_very strong PM2_moderate PM3_moderate | Pathogenic | Pathogenic | One case from Saudi exome project [26] |
| 0-35 | CCDC39 | NM_181426.1 | c.2190del; p.(Glu731Asnfs*31) | 3: 180619334del | 16/20 | Yes | Yes | PVS1_very strong PM2_moderate PM3_moderate | Pathogenic | Pathogenic | Algerian/Tunisian founder effect [27, 39] |
| 0-6 (4 aff) | CCDC40 | NM_017950.3 | c.48A>G; p.(Gly16Gly) | 17: 80038141A>G | 2/20 | No | na | PM2_moderate PM3_supporting PP1_strong | Likely pathogenic (may create splice enhancer) | Likely benign | No |
| 0-36, 0-39 | CCNO | NM_021147.5 | c.381+5G>C | 5: 55233138C>G | 1/3 | No | No | PM2_moderate PM3_moderate PP1_moderate PP3_supporting PP4_supporting | Likely pathogenic | Absent | No |
| 0-16, 0-30, 0-40 | DNAAF4 (DYX1C1) | NM_130810.3 | c.384_390del; p.(Tyr128*) | 15: 55491138_55491144del | 5/10 | Yes | Yes | PVS1_very strong PM2_moderate PM3_moderate | Pathogenic | Likely pathogenic | No |
| 0-4, 0-15, 0-18, 0-26, 0-42 | DNAAF11 (LRRC6) | NM_012472.4 | c.436G>C; p.(Asp146His) | 8: 132632957C>G | 5/12 | No | na | PS3_strong PM3_moderate PP1_strong | Pathogenic | Pathogenic | Two unrelated Palestinian families [28, 40] |
| 0-23 (2 aff) | DNAH5 | NM_001369.2 | c.10050G>A; p.(Trp3350*) | 5: 13766027C>T | 59/79 | Yes | Yes | PVS1_very strong PM2_moderate PM3_supporting | Pathogenic | Absent | No |
| 0-24 | DNAH11 | NM_001277115.1 | c.6727C>T; p.(Arg2243*) | 7: 21710596C>T | 41/82 | Yes | Yes | PVS1_very strong PM3_moderate | Pathogenic | Pathogenic/likely pathogenic | [41] |
| 0-7 | DNAH11 | NM_001277115.1 | c.12646G>T; p.(Glu4216*) | 7: 21892563G>T | 77/82 | Yes | Yes | PVS1_very strong PM2_moderate PM3_moderate | Pathogenic | Absent | No |
| 0-22 | DNAH11 | NM_001277115.1 | c.13240dup; p.(Thr4414Asnfs*34) | 7: 21900057dup | 81/82 | Yes | Yes | PVS1_very strong PM2_moderate PM3_moderate | Pathogenic | Pathogenic | No |
| 0-28 | DNAH11 | NM_001277115.1 | c.13436_13440dup; p.(Tyr4481Leufs*7) | 7: 21901139_21901143dup | 82/82 | Yes | No | PVS1_moderate PM2_moderate PM3_moderate | Likely Pathogenic | Absent | No |
| 0-14, 0-19 | DRC1 | NM_145038.5 | c.1521_1524del; p.(Glu508Alafs*4) | 2: 26450009_26450012del | 12/17 | Yes | Yes | PVS1_strong PM2_moderate PM3_moderate | Likely Pathogenic | Absent | No |
| 0-5 | ODAD3 (CCDC151) | NM_145045.4 | c.850C>T; p.(Gln284*) | 19: 11426257G>A | 7/13 | Yes | Yes | PVS1_strong PM2_moderate PM3_supporting | Likely Pathogenic | Absent | No |
| 0-29 | RSPH4A | NM_001010892.3 | c.367del; p.(Pro123Leufs*44) | 6: 116616991del | 1/6 | Yes | Yes | PVS1_very strong PM2_moderate PM3_supporting | Pathogenic | Absent | No |
| 0-37 | RSPH4A | NM_001010892.3 | c.72G>A; p.(Trp24*) | 6: 116616695G>A | 1/6 | Yes | Yes | PVS1_very strong PM2_moderate PM3_supporting | Pathogenic | Absent | No |
| 0-27, 0-32, 0-33 | RSPH9 | NM_152732.4 | c.800_802del; p.(Lys268del) | 6: 43670922_43670924del | 5/5 | No | na | PS3_strong PM2_supporting PM3_moderate PM4_supporting PP1_strong | Pathogenic | Pathogenic | Two Bedouin families; one Saudi family [29, 30, 42] |
| 0-34 | SPAG1 | NM_172218.3 | c.742C>T; p.(Arg248*) | 8: 100187160C>T | 8/19 | Yes | Yes | PVS1_very strong PM2_moderate PM3_supporting PP1_supporting | Pathogenic | Absent | No |
| 0-3 | CCDC103 | NM_213607.3 | c.104G>C; p.(Arg35Pro) | 17: 44901102G>C | 2/4 | No | na | PM2_moderate PM3_moderate PP3_supporting PP4_supporting | VUS (likely pathogenic) | VUS | No |
| 0-10, 0-12 | DNAH11 | NM_001277115.1 | c.563T>C; p.Met188Thr | 7:21558869T>C | 3/82 | No | na | PM2_moderate PM3_moderate PP1_supporting | VUS | Absent | No |
| 0-17 | DNAL1 | NM_031427.4 | c.285_287del; p.(Glu97del) | 14: 73687283_73687285del | 6/8 | No | No | PM2_moderate PM3_supporting PM4_supporting | VUS | VUS | No |
| 0-13 (**aff+aff father) | RSPH9 | NM_152732.4 | c.760del; p.(Arg254Alafs*76) | 6: 43670878del | 5/5 | Yes | No | PVS1_moderate PM2_moderate PM3_supporting | VUS | Absent | No |
Study ID indicates family number and each family has a single affected child with a positive genetic diagnosis, except where ‘aff’ is shown, indicating that there is more than one affected child in the family (number of affected individuals is shown in these cases). Family 0-13 is the only family with an affected parent in addition to affected children. Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources (DECIPHER), American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP) and ClinVar classifications indicate likelihood that variants cause protein loss of function, transcript nonsense-mediated decay (NMD), in addition to showing their predicted pathogenic, likely pathogenic or variants of unknown significance (VUS) status. LOF: loss of function; na: not applicable (i.e. cannot be done for missense variants).