Table 1.
Genetic and TEM Information in This Cohort
| Patient No. | Gene | Complementary DNA Change (Protein Change) | dbSNP | Type of Mutation | Source | GnomAD, All | ACMG Guideline |
Mutation State | Reference | TEM | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Class | Evidence | ||||||||||
| 1 | CCDC39 | c.1308delG "(p.Q436Hfs∗10) | NA | Frameshift | P | None | Path | PVS1+PM2+PM3 | Compound heterozygous | Current | IDA/CA/MTD |
| c.1167+1G→A (P?02) | rs1292030955 | Splicing | M | None | Path | PVS1+PM2+PP3 | |||||
| 2 | CCDC39 | c.1363-2A→G (P?) | NA | Splicing | P | None | Path | PVS1+PM2+PP3 | Compound heterozygous | Current | IDA/CA/MTD |
| c.210+1G→C (P?) | NA | Splicing | M | None | Path | PVS1+PM2+PP3 | |||||
| 3 | CCDC39 | c.526_c.527delCT (p.L176Afs∗10) | rs780175755 | Frameshift | P | None | Path | PVS1+PS1+PM2 | Compound heterozygous | 23255504 | IDA/CA/MTD |
| c.2542G→T (p.E848X) | NA | Nonsense | M | None | Path | PVS1+PM2+PP3 | |||||
| 4/5 | CCDC39 | c.872delT (p.L291Xfs∗1) | NA | Frameshift | P | None | Path | PVS1+PM2+PP1 | Compound heterozygous | Current | Inadequate/NA |
| c.833_c.834delAG (p.E278Vfs∗2) | NA | Frameshift | M | None | Path | PVS1+PM2+PP1 | |||||
| 6 | CCDC40 | c.961C→T (p.R321X) | rs754867753 | Nonsense | M | None | Path | PVS1+PS1+PM2 | Compound heterozygous | 21131974/current | IDA/CA/MTD |
| c.2330G→A (p.W777X) | NA | Nonsense | P | None | Path | PVS1+PM2+PP3 | |||||
| 7 | CCNO | c.267_c.268insAGCCC (p.V90Sfs∗6) | rs939597472 | Frameshift | P | None | Path | PVS1 +PM2+PM5 | Compound heterozygous | 24747639/current | NA |
| c.940G→T (p.E314X) | NA | Nonsense | M | None | Path | PVS1+PM2+PM3 | |||||
| 8 | CCNO | c.262_c.263insGGCCC (p.Q88Rfs∗8) | rs587777502 | Frameshift | M/P | None | Path | PVS1+PS1+PM2 | Homozygous | 24747639 | NA |
| 9 | CCNO | c.262_c.263insGGCCCGGCCC (p.Q88Rfs∗51) | rs587777502 | Frameshift | P/M | None | Path | PVS1+PM2+PP1 | Homozygous | Current | Oligocilia |
| 10 | DNAAF3 | c.813_c.814insCGAC (p.A272Rfs∗17) | NA | Frameshift | M | None | Path | PVS1+PM2+PP1 | Compound heterozygous | Current | ODA+IDA |
| c.677G→A (p.G226E) | rs1171652733 | Missense | P | None | LP | PM2+PM3+PP2+PP3 | |||||
| 11 | DNAAF3 | c.271C→A (p.P91T) | NA | Missense | P/M | None | LP | PM1+PM2+PP3+PP4 | Homozygous | Current | ODA+IDA |
| 12 | DNAH1 | c.5356C→T (p.R1786C) | rs759042431 | Missense | M | 0.000073 | LP | PM1+PM2+PP3+PP4 | Compound heterozygous | Current | NA |
| c.1286+7C→A (P?) | rs570694571 | Splicing near | P | None | VUS | PM2+BP4 | |||||
| 13 | DNAH1 | c.2912G→A (p.R971H) | rs190420231 | Missense | P | 0.000097 | LP | PM1+PM2+PP3+PP4 | Compound heterozygous | Current | Normal |
| c.11135G→A (p.R3712Q) | rs200395837 | Missense | M | 0.000065 | VUS | PM1+PP4 | |||||
| 14 | DNAH1 | c.2610G→A (p.W870X) | NA | Nonsense | P/M | None | Path | PVS1+PM2+PP3 | Homozygous | 28577616 | NA |
| 15 | DNAH1 | c.3836A→G (p.K1279R) | rs142595873 | Missense | M | 0.0009 | LP | PM1+PM3+PP3+PP1 | Compound heterozygous | 25877616 | NA |
| c.6328_6337del (p.S2110Gfs ∗19) | NA | Frameshift | P | None | Path | PVS1+PM2+PP1 | |||||
| 16 | DNAH11 | c.4321C→T (p.R1441W) | rs183489539 | Missense | P | None | VUS | PM1+PM2+PP3 | Compound heterozygous | Current | Normal |
| c.3025C→G (p.L1009V) | rs542059067 | Missense | M | None | VUS | PM2+PP3 | |||||
| 17 | DNAH11 | c.4670G→T (p.C1557F) | NA | Missense | P | None | LP | PM1+PM2+PP3+PP4 | Compound heterozygous | Current | NA |
| c.9220C→G (p.Q3074E) | rs775542623 | Missense | M | 0.000054 | LP | PM1+PM2+PP3+PP4 | |||||
| 18 | DNAH11 | c.8005C→T (p.Q2669X) | NA | Nonsense | P | None | Path | PVS1+PM2+PP4 | Compound heterozygous | Current | Normal |
| c.13163-2_13163-1insCAAT (P?) | NA | Splicing | M | None | Path | PVS1+PM2+PP4 | |||||
| 19 | DNAH11 | c.3020T→G (p.L1007X) | rs1480698078 | Nonsense | P | None | Path | PVS1+PM2+PP4 | Compound heterozygous | Current | NA |
| c.12934-3_12934-2insG (P?) | NA | Splicing | M | None | Path | PVS1+PM2+PP4 | |||||
| 20 | DNAH11 | c.11383_11386delAGAA (p.K3797Rfs∗2) | NA | Frameshift | De novo | None | Path | PVS+PS2+PM2 | Compound heterozygous | Current | CA |
| c.1942delT (p.W649Gfs∗19) | NA | Frameshift | M | None | Path | PVS1+PM2+PP4 | |||||
| 21 | DNAH11 | c.6165C→G (p.Y2055X) | rs184241449 | Nonsense | M | None | Path | PVS1+PM2+PP3 | Compound heterozygous | Current | Oligocilia |
| c.11924C→T (p.S3975L) | NA | Missense | P | None | LP | PM1+PM2+PM3+PP3 | |||||
| 22 | DNAH11 | c.6632_6633insTGAAC (p.F2214Nfs∗24) | NA | Frameshift | M | None | Path | PVS1+PM2+PP4 | Compound heterozygous | Current | NA |
| c.10053_10054insAA (p.T3352Kfs∗19) | NA | Frameshift | P | None | Path | PVS1+PM2+PP4 | |||||
| 23 | DNAH11 | c.13373C→T (p.P4458L) | rs72658835 | Missense | P | None | Path | PS1+PM1+PM2+PP3 | Compound heterozygous | 22184204 | NA |
| exon21-66del (P?) | NA | Deletion | M | None | Path | PVS1+PM2+PM3 | |||||
| 24 | DNAH11 | c.727A→G (p.I243V) | rs189000268 | Missense | P | 0.0004 | VUS | PM1+PM2+BP4 | Compound heterozygous | Current | Oligocilia |
| c.1452T→G (p.F484L) | rs755256285 | Missense | M | 0.000046 | LP | PM1+PM2+PP3+PP4 | |||||
| 25 | DNAH11 | c.6937C→G (p.R2313G) | NA | Missense | P | None | LP | PM1+PM2+PP1+PP4 | Compound heterozygous | Current | Oligocilia |
| c.5513T→A (p.V1838D) | rs1336120886 | Missense | M | None | LP | PM&+PM2+PP3+PP4 | |||||
| 26 | DNAH11 | c.12153T→A (p.D4051E) | NA | Missense | M | None | VUS | PM2+PP3 | Compound heterozygous | Current | NA |
| c.2485C→T (p.R829C) | rs767607595 | Missense | P | None | VUS | PM2+PP1 | |||||
| 27 | DNAH11 | c.13276T→C (p.W4426R) | rs527548552 | Missense | M | 0.0001 | LP | PM1+PM2+PP1+PP3 | Compound heterozygous | Current | NA |
| c.10433G→A (p.R3478Q) | rs117729990 | Missense | P | 0.0008 | VUS | PP3+PP4 | |||||
| 28 | DNAH11 | c.10851A→T (p.R3617S) | rs373667589 | Missense | P | None | VUS | PM2+PP3+PP4 | Compound heterozygous | Current | NA |
| c.13189C→A (p.H4397N) | rs774489385 | Missense | M | None | LP | PM1+PM2+PP3+PP4 | |||||
| 29 | DNAH11 | c.971C→T (p.A324V) | rs79874320 | Missense | M | 0.0003 | LP | PM1+PM2+PM3 | Compound heterozygous | Current | Oligocilia |
| c.6165C→G (p.Y2055X) | rs184241449 | Nonsense | P | None | Path | PVS1+PM2+PP3 | |||||
| 30 | DNAH11 | c.12679A→G (p.S4227G) | rs574488123 | Missense | P | 0.0002 | VUS | PM2+PP1+PP4 | Compound heterozygous | Current | conical Protrusions |
| c.5523G→A (p.S1841S) | rs750430725 | Missense | M | None | VUS | PM2+PP3+PP4 | |||||
| 31 | DNAH5 | c.997C→T (p.R333X) | rs771956532 | Nonsense | P | 0.000032 | Path | PVS1+PM2 +PP5 | Compound heterozygous | Current | NA |
| c.7918_c.7919insA (p.M2640Nfs∗18) | NA | Frameshift | M | None | Path | PVS1+PM2+PP4 | |||||
| 32 | DNAH5 | c.12813G→A (p.W4271X) | NA | Nonsense | P | None | Path | PVS1+PM2+PP4 | Compound heterozygous | Current | ODA |
| c.5928delA (p.A1977Pfs∗77) | NA | Frameshift | M | None | Path | PVS1+PM2+PP4 | |||||
| 33 | DNAH5 | c.5563_c.5564insA (p.I1855Nfs∗6) | rs752925056 | Frameshift | P | None | Path | PVS1+PM2+PP4 | Compound heterozygous | 11788826 | Inadequate |
| c.4147_c.4148delAinsTCC (p.I1383Sfs∗22) | NA | Frameshift | M | None | Path | PVS1+PM2+PP4 | |||||
| 34 | DNAH5 | c.8029C→T (p.R2677X) | rs775946081 | Nonsense | P | None | Path | PVS1+PM2+PP4 | Compound heterozygous | 16627867 | ODA |
| c.6647delA (p. K2216Rfs∗20) | NA | Nonsense | M | None | Path | PVS1+PM2+PP4 | |||||
| 35 | DNAH5 | c.4114C→G (p.Q1372E) | NA | Missense | M | None | LP | PM1+PM2+PM5+PP3 | Compound heterozygous | Current | ODA |
| gain1 exon37 (P?) | NA | Duplication | De novo | None | Path | PVS1+PM2+PP4 | |||||
| 36 | DNAH5 | c.8383C→T (p.R2795X) | rs560398270 | Nonsense | M | None | Path | PVS1+PM2+PP3 | Compound heterozygous | 30067075/Current | ODA |
| c.8311C→T (p.R2771C) | rs769557047 | Missense | P | None | LP | PM1+PM2+PM3+PP3 | |||||
| 37 | DNAH5 | c.12472C→T (p.R4158W) | rs3756672 | Missense | P | 0.0023 | VUS | PM1+BP6 | Compound heterozygous | Current | NA |
| c.13286G→A (p.R4429Q) | rs61744047 | Missense | M | 0.0023 | VUS | PM1+PP5+BP6 | |||||
| 38 | DNAH5 | c.11023_c.11028+17delTTTAAGGTAGGTTAAACCTATGGinsC (p.F3675_K3676del) | NA | Deletion | De novo | None | LP | PS2+PM2+PM4+PP4 | Compound heterozygous | Current | ODA |
| c.8366A→G (p.H2789R) | NA | Missense | P | None | LP | PS2+PM2+PM3 | |||||
| 39 | DNAH5 | c.9502C→T (p.R3168X) | rs863224504 | Nonsense | P | None | Path | PVS1+PM2+PP4 | Compound heterozygous | Current | NA |
| c.6061+1G→A (P?) | rs772658660 | Splicing | M | None | Path | PVS1+PM2+PP4 | |||||
| 40 | DNAI1 | c.1738G→A (p.D580N) | NA | Missense | P | None | LP | PM1+PM2+PP3+PP4 | Compound heterozygous | Current | ODA |
| c.482C→T (p.T161I) | NA | Missense | M | None | LP | PM1+PM2+PP1+PP4 | |||||
| 41 | DNAI1 | c.1612G→A (p.A538T) | rs368248592 | Missense | P/M | 0.000065 | LP | PS1+PM2+PP3 | Homozygous | Current | ODA |
| 42 | HEATR2 | c.2511G→A (p.S837S) | rs143524894 | Synonymous | P | 0.000016 | VUS | PM2+PP1 | Compound heterozygous | Current | NA |
| c.2420A→G (p.D807G) | rs201177019 | Missense | M | 0.0008 | LP | PM1+PM2+PP1+PP4 | |||||
| 43 | HEATR2 | c.2011G→A (p.A671T) | rs751454661 | Missense | P | 0.0002 | LP | PS4+PM1+PM2 | Compound heterozygous | Current | ODA+IDA |
| c.788G→A (p.R263Q) | rs201059622 | Missense | M | None | VUS | PM1+PM2+PP1 | |||||
| 44 | LRRC6 | exon 8-10 del (P?) | NA | Deletion | P/M | None | Path | PVS1+PM2+PP4 | Homozygous | Current | ODA+IDA |
| 45 | RSPH4A | c.1454G→A (p.R485Q) | rs1296082790 | Missense | P/M | None | VUS | PM2+PP3+PP4 | Homozygous | Current | CA |
| 46 | RSPH9 | c.421G→A (p.V141M) | rs2295947 | Missense | M | 0.0005 | VUS | PM2+PP3+BP1 | Compound heterozygous | Current | CA |
| c.467G→A (p.R156Q) | rs201032669 | Missense | P | None | VUS | PM1+PP3+PP5 | |||||
| 47 | RSPH9 | c.467G→A (p.R156Q) | rs201032669 | Missense | P | None | VUS | PM1+PP3+PP5 | Compound heterozygous | 25789548 | Conical protrusions |
| c.-41T→C (P?) | NA | Non-coding | M | None | VUS | PM2+PP1 | |||||
| 48 | SPAG1 | c.1649_c.1650insA (p.I550Ifs∗10) | NA | Frameshift | P | None | Path | PVS1+PM2+PP4 | Compound heterozygous | Current | ODA+IDA |
| c.691delT (p.Y231Ifs∗12) | NA | Frameshift | M | None | Path | PVS1+PM2+PP4 | |||||
| 49 | CCDC114 | c.-41_2A→C (P?) | rs963154615 | Splicing | P | None | Path | PVS1+PM2+PP3 | Compound heterozygous | Current | NA |
| c.705_c.706insGCAG (p.P236Afs∗11) | rs1294704273 | Frameshift | M | None | Path | PVS1+PM2+PM3 | |||||
| 50 | ARMC4 | c.2306C→A (p.P769H) | rs117515566 | Missense | P | 0.000032 | LP | PM1+PM2+PP3 | Compound heterozygous | Current | ODA |
| c.1679C→T (p.A560V) | rs749814633 | Missense | M | 0.000097 | Path | PS4+PM1+PM2+PP3 | |||||
| 51 | DNAH14 | c.4172 _c.4173insAT (p.R1391Rfs∗26) | rs77953334 | Frameshift | M | 0.0031 | Path | PVS1+PM2+PP4 | Compound heterozygous | Current | IDA |
| c.5068delG (p.G1690Vfs∗12) | rs577893006 | Frameshift | P | 0.0002 | Path | PVS1+PM2+PP4 | |||||
ACMG = American College of Medical Genetics and Genomics; dbSNP = Single Nucleotide Polymorphism Database; GnomAD = Genome Aggregation Database; IDA = inner dynein arm; LP = likely pathogenic; M = maternal; NA = not applicable; ND = not determined; ODA = outer dynein arm; P = paternal; Path = pathogenic; TEM = transmission electron microscopy; VUS = variant of uncertain significance.