Table 5.
High-Impact, Likely Biallelic Variants in 19 Genes in Unsolved Cases
| Individual | Phenotype | Sex | Ethnicity | Gene | Variant genomic | Variant HGVSc | Variant HGVSp | GT | Consequence | Description |
|---|---|---|---|---|---|---|---|---|---|---|
| G001284 | multiple | F | SAS | SCAPER | 15:76998312G>A | ENST00000563290.1; c.2179C>T | p.Arg727Ter | 0/1 | stop_gained | S-phase cyclin A-associated protein in the ER |
| G001284 | multiple | F | SAS | SCAPER | 15:77064214CA>C | ENST00000563290.1; c.1116delT | p.Val373SerfsTer21 | 0/1 | frameshift | S-phase cyclin A-associated protein in the ER |
| G001298 | RD | F | SAS | FUT5 | 19:5867071G>T | ENST00000252675.5; c.666C>A | p.Tyr222Ter | 1/1 | stop_gained | fucosyltransferase 5 (alpha (1,3) fucosyltransferase) |
| G001298 | RD | F | SAS | PODNL1 | 19:14046820C>CAGCT | ENST00000339560.5; c.374_377dupAGCT | p.Gln127AlafsTer119 | 1/1 | frameshift | podocan-like protein 1-like |
| G001411 | RP | M | AFR | NAALADL1 | 11:64812774G>GC | ENST00000358658.3; c.2191dupG | p.Ala731GlyfsTer9 | 0/1 | frameshift | N-acetylated alpha-linked acidic dipeptidase-like 1 |
| G001411 | RP | M | AFR | NAALADL1 | 11:64822078G>A | ENST00000358658.3; c.736C>T | p.Arg246Ter | 0/1 | stop_gained | N-acetylated alpha-linked acidic dipeptidase-like 1 |
| G005002 | CRD | M | SAS | WASF3 | 13:27216381GTGTTTTCAATTTTCAGATTGTGAACCA>G | ENST00000335327.5; c.−10-14_3delTTTTCAATTTTCAGATTGTGAACCATG | NA | 1/1 | splice_acceptor | WAS protein family, member 3 |
| G005019 | Usher | F | SAS | PLD4 | 14:105395186GC>G | ENST00000392593.4; c.388delC | p.Gln130ArgfsTer108 | 0/1 | frameshift | phospholipase D family, member 4 |
| G005019 | Usher | F | SAS | PLD4 | 14:105398102CTGTCCCCA>C | ENST00000392593.4; c.937_944delTGTCCCCA | p.Cys313GlyfsTer167 | 0/1 | frameshift | phospholipase D family, member 4 |
| G005203 | RP | F | SAS | FAM71A | 1:212799206T>TGCAG | ENST00000294829.3; c.991_994dupGGCA | p.Thr332ArgfsTer88 | 1/1 | frameshift | family with sequence similarity 71, member A |
| G005251 | cone dystrophy | M | SAS | POMZP3 | 7:76240807T>TG | ENST00000310842.4; c.538dupC | p.Gln180ProfsTer14 | 1/1 | frameshift | POM121 and ZP3 fusion |
| G005492 | RP | F | EUR | IRX5 | 16:54967694CTAAAG>C | ENST00000394636.4; c.1362_1366delTAAAG | p.Lys455ProfsTer19 | 1/1 | frameshift | iroquois homeobox 5 |
| G005513 | Stargardt | M | EUR | ITIH2 | 10:7776934CT>C | ENST00000358415.4; c.1838delT | p.Leu613ArgfsTer5 | 0/1 | frameshift | inter-alpha-trypsin inhibitor heavy chain 2 |
| G005513 | Stargardt | M | EUR | ITIH2 | 10:7780709CAT>C | ENST00000358415.4; c.2084_2085delAT | p.His695ArgfsTer5 | 0/1 | frameshift | inter-alpha-trypsin inhibitor heavy chain 2 |
| G005514 | RP | M | AFR | SLC37A3 | 7:140064249G>A | ENST00000326232.9; c.334C>T | p.Arg112Ter | 1/1 | stop_gained | solute carrier family 37, member 3 |
| G007696 | CRD | M | SAS | NUMB | 14:73746066G>GC | ENST00000355058.3; c.1162dupG | p.Ala388GlyfsTer6 | 1/1 | frameshift | numb homolog (Drosophila) |
| G007696 | CRD | M | SAS | FAM57B | 16:30038139GC>G | ENST00000380495.4; c.234delG | p.Gln79AsnfsTer43 | 1/1 | frameshift | family with sequence similarity 57, member B |
| G007723 | RP | M | SAS | FOXI2 | 10:129536034AC>A | ENST00000388920.4; c.498delC | p.Asp166GlufsTer87 | 1/1 | frameshift | forkhead box I2 |
| G008152 | RP | M | EUR | CROCC | 1:17292217G>A | ENST00000375541.5; c.4406−1G>A | NA | 1/1 | splice_acceptor | ciliary rootlet coiled-coil, rootletin |
| W000146 | RP | F | EUR | CCZ1B | 7:6844600C>A | ENST00000316731.8; c.1075G>T ENST00000375541.5; c.4406−1G>A |
p.Glu359Ter | 1/1 | stop_gained | CCZ1 vacuolar protein trafficking and biogenesis associated homolog B (S. cerevisiae) |
| W000278 | other | F | SAS | OR2M7 | 1:248487484AG>A | ENST00000317965.2; c.386delC | p.Pro129LeufsTer2 | 1/1 | frameshift | olfactory receptor, family 2, subfamily M, member 7 |
| W000375 | RP | M | SAS | PRTFDC1 | 10:25231367T>C | ENST00000320152.6; c.49−2A>G | NA | 1/1 | splice_acceptor | phosphoribosyl transferase domain containing 1 |
| W000375 | RP | M | SAS | UBAP1L | 15:65395024T>G | ENST00000559089.1; c.121−2A>C | NA | 1/1 | splice_acceptor | ubiquitin associated protein 1-like |
Genomic coordinates refer to genome build GRCh37. Analysis is limited to cases that underwent WGS in whom pathogenic variants in known genes were not detected and whose family history is not inconsistent with recessive inheritance of disease. Abbreviations: RP, retinitis pigmentosa; RD, retinal dystrophy; CRD, cone-rod dystrophy; other, any phenotype with frequency of fewer than eight individuals; multiple, more than one phenotype including syndromic cases.