Table 2 Potentially causative variants identified by WES in children with MIS-C
Patient | Gene (Location) | Mutation type | Mutation description (GRCh38/hg38) | Status | MAF (GnomAD genomes/ ABraOM) | Gene function | Inheritance pattern (OMIM) * | Conclusion (ACMG parameters) ** |
|---|---|---|---|---|---|---|---|---|
EXOC1 | FREM1 (9p22.3) | Nonsense | Chr9:14808083G > T NM_001379081.2 c.2945C > A:p.Ser982* r377212852 | Heterozygous | 0.003%/NA | FRAS1 related extracellular matrix 1 | AR/AD | Pathogenic (PVS1, PM2) |
EXOC3 | MPO (17q22) | Splice acceptor | Chr17:58270865 T > G NM_000250.2 c.2031-2A > C rs35897051 | Heterozygous | 0.5%/0.2% | Myeloperoxidase | AR/AD | Pathogenic (PVS1, PM2, PP5, PS3) |
POLG (15q26.1) | Missense | Chr15:89323423A > G NM_002693.3 c.2246 T > C:p.Phe749Ser rs202037973 | Heterozygous | 0.02%/NA | DNA polymerase gamma, catalytic subunit | AR/AD | VUS (PM2, PP3) | |
EXOC5 | C6 (5p13.1) | Frameshift | Chr5:41176504G > T NM_000065.5 c.1138delC:p.Gln380fs rs375762365 | Heterozygous | 0.2%/0.04% | Complement C6 | AR with reported cases of heterozygous case with reduced C6 levels | Pathogenic (PVS1, PM2, PP5) |
EXOC6 | ABCA4 (1p22.1) | Missense | Chr1:94021934A > G NM_000350.3 c.4685 T > C:p.Ile1562Thr rs1762111 | Heterozygous | 0.01%/0.04% | ATP binding cassette subfamily A member 4 | AR/AD | VUS (PM2, PP2, PP3) |
EXOC13 | ABCA4 (1p22.1) | Missense | Chr1:94001992C > G NM_000350.3 c.6149G > C:p.Val2050Leu rs41292677 | Heterozygous | 0.4%/0.3% | ATP binding cassette subfamily A member 4 | AR/AD | Pathogenic (PM1, PM2, PP3, PP2, PP5) |
EXOC14 | ABCA4 (1p22.1) | Missense | Chr1:94098885C > A NM_000350.3 c.677G > T:p.Arg226Leu rs144310835 | Heterozygous | 0.2%/0.08% | ATP binding cassette subfamily A member 4 | AR/AD | VUS (PM2, PP2) |
EXOC15 | C9 (5p13.1) | Nonsense | Chr5:39342112G > T NM_001737.5 c.162C > A:p.Cys54* rs34000044 | Heterozygous | 0.06%/0.04% | Complement C9 | UN | Pathogenic (PVS1, PM2, PP5) |
EXOC16 | ABCC6 (16p13.11) | Missense | Chr16:16154974G > A NM_001171.6 c.3940C > T:p.Arg1314Trp rs63750759 | Heterozygous | 0.08%/0.1% | ATP binding cassette subfamily C member 6 | AR/AD | Pathogenic (PP5, PM1, PM2, PM5, PP2, PP3) |
EXOC18 | BSCL2 (11q12.3) | Frameshift | Chr11:62694680G > GT NM_001122955.4 c.517dupA:p.Thr173fs rs786205071 | Heterozygous | NA/NA | BSCL2 lipid droplet biogenesis associated, seipin | AR/AD | Pathogenic (PVS1, PM2, PP5) |