Determination of pathogenicity of missense mutations
| Sample ID | Gene | cDNA change | Amino acid change | Zygosity | ACMG | ClinVar | Varsome | EVE prediction | Final verdict* |
| FA-02 | FANCJ (BRIP1) | NM_032043.3:c.1878A>T | p.Glu626Asp | Homozygous | Likely pathogenic | VUS | Pathogenic | Pathogenic | Pathogenic |
| FA-02/21 | FANCA | NM_000135.4:c.3788T>C | p.Phe1263Ser | Compound heterozygous | Likely pathogenic | VUS | Likely pathogenic | VUS | VUS/likely pathogenic |
| FA-02/21 | FANCA | NM_000135.4:c.1540G>A | p.Ala514Thr | Compound heterozygous | VUS | NA | VUS | Pathogenic | Pathogenic |
| FA-03 | FANCA | NM_000135.4:c.2786A>C | p.Tyr929Ser | Compound heterozygous | Likely pathogenic | VUS | VUS | Pathogenic | Pathogenic† |
| FA-05 | FANCA | NM_000135.4:c.1304G>A | p.Arg435His | Homozygous | Pathogenic | Pathogenic | Pathogenic | Pathogenic | Pathogenic |
| FA-06/20 | FANCA | NM_000135.4:c.4198C>T | p.Arg1400Cys | Homozygous | Likely pathogenic | Pathogenic | Pathogenic | Pathogenic | Pathogenic |
| FA-12 | FANCA | NM_000135.4:c.1303C>T | p.Arg435Cys | Compound heterozygous | Pathogenic | Pathogenic | Likely pathogenic | Pathogenic | Pathogenic |
| FA-18 | FANCA | NM_000135.4:c.2852G>C | p.Arg951Pro | Homozygous | Pathogenic | NA | Likely pathogenic | Pathogenic | Pathogenic |
| FA-18/21 | FANCA | NM_000135.4:c.2290C>T | p.Arg764Trp | Homozygous | VUS | Pathogenic | Pathogenic | Pathogenic | Pathogenic |
| FA-21/21 | FANCA | NM_000135.4:c.3239G>A | p.Arg1080Gln | Homozygous | Likely pathogenic | Likely pathogenic | Likely pathogenic | Pathogenic | Pathogenic |
| FA-31/21 | FANCA | NM_000135.4:c.1430T>C | p.Leu477Ser | Homozygous | VUS | NA | Pathogenic | Pathogenic | Pathogenic |
| FA-38 | FANCG | NM_004629.2:c.425T>C | p.Leu142Pro | Compound heterozygous | VUS | NA | VUS | Pathogenic | Pathogenic |
| FA-5/21 | UBE2T/FANCT | NM_014176.4:c.232A>C | p.Asn78His | Homozygous | VUS | NA | VUS | Pathogenic | Pathogenic |
| FA-527 | FANCC | NM_000136.3:c.1585A>C | p.Thr529Pro | Homozygous | VUS | VUS | VUS | Pathogenic | Pathogenic† |
| FA-533 | FANCA | NM_000135.4:c.3934G>A | p.Asp1312Asn | Compound heterozygous | Likely pathogenic | NA | VUS | Pathogenic | Pathogenic |
| FA-573 | FANCA | NM_000135.4:c.2T>A | p.Met1Lys | Compound heterozygous | Pathogenic | Likely pathogenic | Pathogenic | Not available | Pathogenic |
| FA-593 | FANCA | NM_000135.4:c.2851C>T | p.Arg951Trp | Homozygous | Likely pathogenic | Pathogenic | Likely pathogenic | Pathogenic | Pathogenic |
| FA-637/18 | FANCJ (BRIP1) | NM_032043.3:c.751C>T | p.Arg251Cys | Homozygous | VUS | Conflicting | Likely pathogenic | Pathogenic | Pathogenic |
| FA-641/18 | FANCF | NM_022725.4:c.41T>G | p.Leu14Arg | Homozygous | VUS | NA | VUS | VUS | Pathogenic† |
| FA-646/18 | FANCA | NM_000135.4:c.2852G>A | p.Arg951Gln | Homozygous | Likely pathogenic | Pathogenic | Likely pathogenic | Pathogenic | Pathogenic |
| FA-649/18 | BRCA2 | NM_000059.4:c.92G>C | p.Trp31Ser | Homozygous | Pathogenic | NA | Likely pathogenic | Not available | Pathogenic |
| FA-652/18 | FANCA | NM_000135.4:c.3163C>T | p.Arg1055Trp | Homozygous | Pathogenic | Pathogenic | Likely pathogenic | Pathogenic | Pathogenic |
| FA-659/18 | FANCA | NM_000135.4:c.3689T>C | p.Leu1230Pro | Homozygous | VUS | NA | VUS | Pathogenic | Pathogenic |
| P-177 | FANCA | NM_000135.4:c.3350G>C | p.Arg1117Thr | Homozygous | Likely pathogenic | Pathogenic | Likely pathogenic | Pathogenic | Pathogenic |
Pathogenic—disease-causing.
*Final verdict considering all the pathogenicity prediction methods.
†Confirmed by complementation.
EVE, evolutionary model of variant effect; NA, not applicable; VUS, Variants of uncertain significance.