Table 2.
Disease-causing variants and CNVs identified in the skeletal ciliopathy cohort
| Family | Gene | Nucleotide | Amino acid/mRNA | Inheritance | Previously reported | Genomic coordinates | MAF# |
|---|---|---|---|---|---|---|---|
| Patients with clinical diagnoses of SRPS and ATD | |||||||
| 1 | DYNC2H1 | c.7919 T > C | p.(Ile2640Thr) | P | [41] | chr11:g.103070036 | – |
| c.9865 G > A | p.(Asp3289Asn) | M | [8] | chr11:g.103114446 | 0.000003 | ||
| c.12602 C > T | p.(Ser4201Phe) | M | VCV000558738.1 ClinVar | chr11:g.103327017 | 0.000169 | ||
| 2 | DYNC2H1 | c.8003 T > G | p.(Val2668Gly) | P | – | chr11:g.103070120 | 0.000009 |
| c.9044 A > G | p.(Asp3015Gly) | M | [42] | chr11:g.103091449 | 0.000774 | ||
| 3 | DYNC2H1 | c.6910 G > A | p.(Ala2304Thr) | P | [8] | chr11:g.103058085 | 0.000697 |
| c.8444 G > A | p.(Ser2815Asn) | M | – | chr11:g.103075683 | – | ||
| 4 | DYNC2H1 | c.5971 A > T | p.(Met1991Leu) | M/P | [42] | chr11:g.103048381 | – |
| c.11284 A > G | p.(Met3762Val) | M/P | [42] | chr11:g.103175330 | 0.003237 | ||
| 5 | DYNC2H1 | c.5682_5683del | p.(His1896Tyrfs*9) | M | [43] | chr11:g.103046971-2 | 0.000179 |
| c.5771 A > T | p.(Asp1924Val) | P | – | chr11:g.103047060 | – | ||
| 6 | DYNC2H1 | c.729 T > A | p.(Tyr243*) | P | – | chr11:g.102987406 | – |
| c.9044 A > G | p.(Asp3015Gly) | M | [42] | chr11:g.103091449 | 0.000774 | ||
| 7 | DYNC2H1 | c.1855C > T | p.(Gln619*) | P | – | chr11:g.102996022 | 0.000105 |
| c.9044 A > G | p.(Asp3015Gly) | M | [42] | chr11:g.103091449 | 0.000774 | ||
| 8 | DYNC2H1 | c.2386del | p.(Arg796Glyfs*8) | M | – | chr11:g.103006489 | 0.000018 |
| c.10163 C > T | p.(Pro3388Leu) | P | VCV000439631.4 ClinVar | chr11:g.103124113 | 0.000140 | ||
| 9 | DYNC2H1 | c.624_625delGTinsAA | p.(Phe209Ile) | P | [44] | chr11:g.102987301-2 | 0.000157 |
| c.2574 + 1 G > A | p.(?) | M | – | chr11:g.103006678 | – | ||
| 10 | DYNC2H1 | c.7129 T > G | p.(Phe2377Val) | M | – | chr11:g.103058304 | – |
| c.6478-16 G > A | r.6477_6478ins6478-14_6478-1 | P | – | chr11:g.103055609 | 0.000018 | ||
| 11 | DYNC2H1 | c.1306 G > T | p.(Glu436*) | P | [22] | chr11:g.102991711 | – |
| c.11070 G > A | r.11044_11116del | M | – | chr11:g.103158288 | 0.000033 | ||
| 12 | DYNC2H1 | c.1366 C > T | p.(Arg456*) | P | – | chr11:g.102992106 | 0.000059 |
| c.3455 T > C | p.(Phe1152Ser) | M | – | chr11:g.103025332 | – | ||
| c.5690 T > C | p.(Ile1897Thr) | M | VCV000864089.1 ClinVar | chr11:g.103046979 | 0.000175 | ||
| c.8354 C > A | p.(Ala2785Glu) | M | – | chr11:g.103075593 | 0.000076 | ||
| 13 | C2CD3 | c.5227 G > T | p.(Gly1743Cys) | P | [36] | chr11:g.73760516 | 0.000163 |
| c.5267 G > A | p.(Gly1756Glu) | M | [35] | chr11:g.73760476 | 0.000062 | ||
| 14 | KIAA0753 | c.810 C > T | r.719_825del | M/P | – | chr17:g.6528090 | 0.000296 |
| 15 | KIAA0753 | c.810 C > T | r.719_825del | M/P | – | chr17:g.6528090 | 0.000296 |
| 16 | KIAA0753 | c.970 C > T | p.(Arg324*) | M/P | [12] | chr17:g.6526336 | 0.000033 |
| 17 | TTC21B | c.2758-2 A > G | p.(?) | M | [12, 39] | chr2:g.166756392 | 0.000039 |
| c.3857 T > C | p.(Ile1286Thr) | P | – | chr2:g.166732691 | 0.000028 | ||
| 18 | WDR19 | c.56 T > G | p.(Phe19Cys) | M | – | chr4:g.39187395 | 0.000029 |
| c.3868_3871del | p.(Thr1290Cysfs*14) | P | – | chr4:g.39279778-81 | 0.000019 | ||
| 19 | WDR19 | c.974 T > C | p.(Leu325Ser) | P | – | chr4:g.39217473 | – |
| c.3758 G > A | p.(Cys1253Tyr) | M | – | chr4:g.39278681 | 0.000065 | ||
| 20 | IFT74 | NC_000009.11: g.26959922_26962969delinsTTA | r.-19_120del | M/P | – | – | – |
| Patient with a clinical diagnosis of CED | |||||||
| 21 | WDR19 | c.1623C > G | p.(Tyr541*) | NA | – | chr4:g.39226647 | 0.000043 |
| c.3533 G > A | p.(Arg1178Gln) | NA | [45] | chr4:g.39274649 | 0.000388 | ||
| Patients with clinical diagnoses of EVC | |||||||
| 22 | EVC | c.1018 C > T | p.(Arg340*) | P | [46] | chr4:g.5749953 | 0.000138 |
| c.175-9 G > A | r.174_175ins175-7_175-1 | M | – | chr4:g.5720966 | 0.000062 | ||
| 23 | EVC2 | c.571 A > G | p.(Asn191Asp) | M/P | – | chr4:g.5691019 | – |
| 24 | PRKACA | c.409 G > A | p.(Gly137Arg) | de novo | [14] | chr19:g.14211648 | – |
| Patients with unclassified skeletal ciliopathies | |||||||
| 25 | DYNC2H1 | c.10022 C > G | p.(Pro3341Arg) | P | – | chr11:g.103116062 | – |
| NC_000011.10: g.103016481_103177263del | p.(Ser901Argfs*1?) | M | – | – | – | ||
| 26 | – | NC_000001.11: g.169095250_175778910del | 1q24q25 deletion | de novo | [40] | – | – |
–, absent; #, gnomAD v2.1.1 and gnomAD v2 SVs
Reference sequences and genomic coordinates according to hg19 [GRCh37]: C2CD3 (NM_015531.5), DYNC2H1 (NM_001080463.1), EVC (NM_001306090.1), EVC2 (NM_147127.4), IFT74 (NM_025103.2), KIAA0753 (NM_014804.2), PRKACA (NM_002730.4); TTC21B (NM_024753.5), WDR19 (NM_025132.3)
ATD asphyxiating thoracic dystrophy, CED cranioectodermal dysplasia, chr chromosome, EVC Ellis-van Creveld syndrome, MAF minor allele frequency (Popmax), M maternal, M/P homozygous variant, NA not available, P paternal, SRPS short-rib polydactyly syndrome