Table 1 Concurrent detection of episignatures (SVM-based) and underlying genomic variants. The seven first columns of the table describe patient characteristics and (likely) pathogenic genomic variants or VUS (marked by a “?”) detected by standard of care methods. The next column indicates the result of the SVM-based classifier for each sample. Patients for which no episignature is identified by the classifiers are classified as control (italic). The last column specifies the ranking of the underlying genomic variant in the fast track analysis of a phenotype-drive prioritization tool (Geneyx) [18]. For the variants prioritized in a subanalysis, both the subanalysis (structural variant (SV) or X-linked (XL)) and the ranking in the subanalysis are provided. *Manual curation of the gene was needed for the identification of this mosaic variant given Clair3 was targeting heterozygous SNVs
From: Clinical evaluation of long-read sequencing-based episignature detection in developmental disorders
Study ID | Age | Sex | Gene | Transcript | Variant | Syndrome | SVM classifier result | SV/SNV ranking |
|---|---|---|---|---|---|---|---|---|
EPI_01 | 12 | F | KMT2D | NM_003482.4 | c.8311C > T p.(Arg2771*) | Kabuki | Kabuki | 1 |
EPI_02 | 24 | F | KMTD2 | NM_003482.4 | c.8304_8307del p.(Ser2768Argfs*18) | Kabuki | Kabuki | 1 |
EPI_03 | 7 | M | NSD1 | NM_022455.5 | c.6188 T > C p.(Leu2063Pro) | Sotos | Sotos | 1 |
EPI_04 | 6 | M | NSD1 | NM_022455.5 | c.3659_3660del p.(Glu1220Alafs*5) | Sotos | Sotos | 1 |
EPI_05 | 11 | M | KMT2A | NM_001197104.2 | c.6571C > T p.(Arg2191*) | Wiedemann-Steiner | Wiedemann-Steiner | 1 |
EPI_06 | 22 | M | KMT2A | NM_001197104.2 | c.10168C > T p.(Gln3390*) | Wiedemann-Steiner | Wiedemann-Steiner | 1 |
EPI_07 | 14 | F | SMC3 | NM_005445.4 | c.720_722del p.(Asp240del) | Cornelia de Lange | Cornelia de Lange | 3 |
EPI_08 | 46 | M | KMT2D | NM_003482.4 | c.16517_16518del p.(Glu5506Glyfs*5) | Kabuki | Kabuki | 1 |
EPI_09 | 2 | M | NSD1 | NM_022455.5 | c.4905C > G p.(Cys1635Trp) | Sotos | Sotos | 1 |
EPI_10 | 5 | M | KMT2A | NM_001197104.2 | c.3460C > T p.(Arg1154Trp) | Wiedemann-Steiner | Wiedemann-Steiner | 1 |
EPI_11 | 5 | M | SMC3 | NM_005445.4 | c.2166_2167insCCCGAG p.(Glu722_Thr723insProGlu) | Cornelia de Lange | Cornelia de Lange | 4 |
EPI_12 | 13 | F | SMARCA2 | NM_003070.5 | c.3476G > A p.(Arg1159Gln) | Nicolaides-Baraitser | Nicolaides-Baraitser | 1 |
EPI_13 | 15 | F | PHF6 | NM_001015877.2 | c.306del p.(Tyr103Thrfs*40) | Börjeson-Forssman-Lehmann | control | 1 |
EPI_14 | 14 | F | KANSL1 | NM_015443.4 | c.1419dup p.(Arg474Thrfs*3) | Koolen-De Vries | Koolen-De Vries | 1 |
EPI_15 | 2 months | M | EHMT1 | NM_024757.5 | c.3717-2A > G | Kleefstra | Kleefstra | 2 |
EPI_16 | 3 | M | chr7:g.72900001_76430000del | Williams-Beuren | Williams Beuren | SV: 1 | ||
EPI_17 | 4 | M | EP300 | NM_001429.4 | g.41168065_41171580del | Rubinstein-Taybi | Rubinstein-Taybi | SV: 1 |
EPI_18 | 3 | M | ZNF711 | NM_001330574.2 | c.1361A > G p.(His454Arg) | MRX97? | control | 4 |
EPI_19 | 3 | M | KMT2D | NM_003482.4 | c.3002_3005del p.(Leu1001Profs*15) | Kabuki | Kabuki | Absent* |
ATRX | NM_000489.6 | c.7263_7265del p.(Gln2425del) | ATRX? | XL: 1 | ||||
EPI_20 | 5 | M | UBE2A | NM_003336.4 | c.19C > T p.(Arg7Trp) | MRXSN | control | 2 |