Table 1 Characterization of 21 parental somatic mosaic variants identified in peripheral blood using clinical ES at BG
Gene | Variant | ACMG variant classification | Proband phenotype | Inheritance mode | Parental mosaicism | Level of mosaicism in ES (%) | Level of mosaicism in NGS (%) | Level of mosaicism in ddPCR |
|---|---|---|---|---|---|---|---|---|
CACNA1C | c.694G > C | VUS | Timothy Syndrome [MIM:601005] | AD | Maternal | 1 | 2 | NA |
COL6A3 | c.218A > G | VUS | Bethlem myopathy [MIM:58810] | AD/AR | Maternal | 0.4 | 0.3 | NA |
COL11A1 | c.3816 + 2dupT | Pathogenic | Stickler Syndrome 2: [MIM:604841] | AD/AR | Maternal | 2.8 | 0.2 (HC) | NA |
DLL4 | c.586G > A | Likely pathogenic | Adams-Oliver syndrome [MIM:616589] | AD | Paternal | 2 | 2 | 0.05% |
HUWE1 | c.12257G > A | Likely pathogenic | Mental retardation, X-linked, turner type [MIM:30076] | XL | Maternal | 0.3 | 0.1 | NA |
IFT172 | c.4161-1G > A | Pathogenic | Retinitis pigmentosa [MIM:616394] | AR | Paternal | 3 | 4 | 3.8% |
KIF1A | c.1132C > T | VUS | Polyhydramnios | AD/AR | Maternal | 2 | 4 | 3.7% |
KIF1A | c.757G > A | Pathogenic | Mental retardation, autosomal dominant 9 [MIM:614255] | AD/AR | Paternal | 1 | 0.1 | NA |
NRXN2 | c.3382G > A | VUS | Autism spectrum disorder | AD | Maternal | 5 | 6 | 4.5% |
PDCD10 | c.474 + 5G > A | Pathogenic | Cerebral cavernous malformations 3 [MIM:603285] | AD | Paternal | 1 | 5 | NA |
PIGA | c.986T > C | Likely pathogenic | Multiple congenital anomalies-hypotonia-seizures syndrome 2 [MIM:300868] | XLR | Maternal | 2 | 2 | 1.83% |
PTEN | c.542T > C | Pathogenic | Cowden syndrome 1 [MIM:158350] | AD | Maternal | 2 | 0.3 | NA |
PTPN11 | c.923A > G | Pathogenic | Noonan syndrome 1 [MIM:163950] | AD | Maternal | 1 | 0.3 | NA |
PTPN11 | c.923A > G | Pathogenic | Noonan syndrome 1 [MIM:163950] | AD | Maternal | 1 | 0.3 | NA |
PTPN11 | c.922A > G | Pathogenic | Noonan syndrome 1 [MIM:163950] | AD | Maternal | 1 | 0.3 | NA |
RBFOX1 | c.474 + 6T > C | VUS | Autism spectrum disorder | AD | Paternal | 1 | 0.2 | NA |
SMARCA2 | c.2254G > A | Likely pathogenic | Nicolaides-Baraister syndrome [MIM:601358] | AD | Paternal | 1 | 0.08 | NA |
SMARCA4 | c.2936G > A | Pathogenic | Coffin Siri syndrome 4 [MIM: 614609] | AD | Paternal | 4 | 5 | 4.76% |
TPM1 | c.475G > A | Likely pathogenic | Cardiomyopathy [MIM:115196] | AD | Paternal | 2 | 0.1 | NA |
USP7 | c.238A > T | Likely pathogenic | Intellectual disability and autism spectrum disorder [PMID: 26365382] | AD | Maternal | 3 | 9 | 4.13 |
ZBTB20 | c.1916G > A | Likely pathogenic | Primrose syndrome [MIM:259050] | AD | Paternal | 1 | 3 | NA |