Table 2.
Variant summary and ACMG/AMP classification of FBXW7 variants identified in this cohort
| Case | Variant (NM_001349798.2) | Protein | Domain | Inheritance | gnomAD v4.1 | ClinVar accession | ACMG/AMP criteria | Classification |
|---|---|---|---|---|---|---|---|---|
| 1 | c.1886_1887insATGCTGTGACCTG | p.(Cys629Ter) | WD40 | De novo | Absent | Not submitted | PVS1, PS2, PM2 | Pathogenic |
| 2 | c.670 C > T | p.(Arg224Ter) | - | De novo | Absent | VCV001722937 (Pathogenic) | PVS1, PS2, PM2 | Pathogenic |
| 3 | c.2020 C > T | p.(Arg674Trp) | WD40 | De novo | Absent | VCV001703001 (Pathogenic) | PS1, PS2, PM1, PM2, PP3 | Pathogenic |
| 4 | c.2066G > A | p.(Arg689Gln) | WD40 | De novo | 6.8 × 10⁻⁷ | VCV001702999 (Pathogenic) | PS1, PS2, PM1, PM2_Supporting, PP3 | Pathogenic |
| 5 | c.2020 C > T | p.(Arg674Trp) | WD40 | De novo | Absent | VCV001703001 (Pathogenic) | PS1, PS2, PM1, PM2, PP3 | Pathogenic |
| 6 | c.1267G > A | p.(Gly423Arg) | WD40 | De novo | Absent | VCV001702998 (Pathogenic) | PS1, PS2, PM1, PM2, PP3 | Pathogenic |
| 7 | c.1922 C > G | p.(Ser641Ter) | WD40 | Maternal | Absent | Not submitted | PVS1, PM2 | Likely Pathogenic |
Variants are annotated on transcript NM_001349798.2 (HGVS nomenclature). Classification follows ACMG/AMP guidelines [27]; criteria codes are defined therein. Allele frequencies are reported from gnomAD v4.1. '–' indicates variant not located within a defined functional domain. Abbreviations: DD, dimerization domain; WD40, WD40 repeat domain; HGVS, Human Genome Variation Society; ACMG/AMP, American College of Medical Genetics and Genomics / Association for Molecular Pathology