Table 1.
Variants identified in C2CD3 in Families 1, 2, and 3
| Chr.11 position | cDNA variant | RNA variant | Protein variant | Location | Genotype | Inheritance | gnomAD MAF | dbSNP ID | In silico predictions & conservation | ACMG classification |
|---|---|---|---|---|---|---|---|---|---|---|
| Family 1, proband | ||||||||||
| 73834032 | c.1365+1G>A | r.1217_1365del | p.Ser406Argfs*23 | Intron 8 | Het | Paternal | 0.000004 | NR | Predicted loss of donor: SpliceSiteFinder-like, MaxEntScan, NNSPLICE, human splicing finder | Pathogenic |
| 73768446 | c.5090+5G>C | r.4951_5090del | p.Ser1652Tyrfs*26 | Intron 25 | Het | Maternal | NR | NR | Predicted loss of donor: SpliceSiteFinder-like, MaxEntScan, NNSPLICE | Pathogenic |
| Family 2, proband | ||||||||||
| 73811607 | c.2695G>A | NA | p.(Val899Met) | Exon 15 | Het | Paternal | NR | NR | GV/GD Score: 65.28/20.52 SIFT: deleterious Polyphen2: probably damaging Mutation taster: disease causing Highly conserved amino acid |
Likely pathogenic |
| 73804863 | c.3342C>T | r.3160_3344del | p.Gly1054Aspfs*7 | Exon 18 | Het | Maternal | 0.000004 | rs147520824 | Predicted loss of donor: SpliceSiteFinder-like, MaxEntScan, NNSPLICE, GeneSplicer | Pathogenic |
| Family 3, proband | ||||||||||
| 73879586 | c.128T>G | NA | p.(Leu43Arg) | Exon 2 | Het | Paternal | NR | NR | GV/GD Score: 353.86/0.00 SIFT: deleterious Polyphen2: probably damaging Mutation taster: disease causing Highly conserved amino acid across mammals |
Likely pathogenic |
| 73760516 | c.5227G>T | NA | p.(Gly1743Cys) | Exon 27 | Het | Maternal | 0.000004 | NR | GV/GD Score: 0.00/158.23 SIFT: deleterious Polyphen2: Prob. damaging Mutation taster: disease causing Highly conserved amino acid |
Pathogenic |
Chr chromosome, Het heterozygous, MAF minor allele frequency, NA not available, NR not reported
Data are annotated using hg19, NM_001286577.1, NG_041791.1