Table 2.
Phenotypic and genotypic details of index cases with disease-causing variants in known disease-associated genes
| ID | Sex (determined genetically) | Gene (transcript) | Chromosomal position (hg19) | Nucleotide and amino acid change | Inheritance | Zygosity/heteroplasmy grade | gnomAD v.2.1.1 MAFa | Genetic diagnosis (MIM phenotype number) | Classification according to applied ACMG criteria/CNV scoreb | Individual ID in LOVDc |
|---|---|---|---|---|---|---|---|---|---|---|
| HN-F142-II-1 | M | KMT2D (NM_003482.3) | chr12:49433509-49433509 | c.8044C>T p.(Gln2682∗) |
de novo | heterozygous | - | Kabuki syndrome 1 (147920) | Pathogenic PVS1, PS2, PM2, PP3 |
00435638 |
| HN-F83-II-1 | M | KMT2D (NM_003482.3) | chr12:49427394-49427395 | c.11093dup p.(Phe3699Leufs∗14) |
de novo | heterozygous | - | Kabuki syndrome 1 (147920) | Pathogenic PVS1, PS2, PM2 |
00435656 |
| HN-F1249-II-1 | F | NSD1 (NM_022455.4) | chr5:176637649-176637650 | c.2256_2257del p.(Pro753Lysfs∗11) |
de novo | heterozygous | - | Sotos syndrome (117550) | Pathogenic PVS1, PM2, PP2 |
00435657 |
| HN-F1406-II-1 | M | Chr7p15.3-p21.2 del (-) | Approx. chr7:15405139-21985421 | 7736 kb deletion (including TWIST1) | de novo | heterozygous | - | Saethre-Chotzen syndrome (101400) | Pathogenic (1,45) | 00435659 |
| HN-F163-II-1 | M | MT-TL1 (NC_012920.1) | chrM:3243-3243 | m.3243A>G | maternal | 13% | - | MELAS syndrome (590050) | Pathogenic PS2_very strong, PS4_strong |
00435658 |
ACMG, American College of Medical Genetics and Genomics; CNV, copy number variation; F, female; ID, identity; LOVD, Leiden Open Variation Database; M, male; MAF, minor allele frequency.
b
Variant is classified as likely pathogenic/pathogenic as per ACMG and amendments 18,19.