Table 6. Patients with pathogenic or likely pathogenic variants in biallelic cancer predisposition genes.
| Diagnosis | Gene | Variant | Protein | CADD-PHRED score |
|---|---|---|---|---|
| Acute myeloid leukemia1 | ADA | c.646G>A | p.(Gly216Arg) | 28.0 |
| Precursor B-cell acute lymphoblastic leukemia | ADA | c.1078+2T>A | p.(?) | 22.9 |
| Chronic myeloid leukemia | ATR | c.2320dupA | p.(Ile774Asnfs*3) | 20.1 |
| Rhabdomyosarcoma | EFL1 | c.159+3A>G | p.(?) | 14.84 |
| Precursor T-cell acute lymphoblastic leukemia | EFL1 | c.2430_2431delCC | p.(Leu811Asnfs*10) | 15.9 |
| Wilms tumor | ERCC3 | c.1115_1120dupAGCAGT | p.(Trp374*) | 37.0 |
| Astrocytoma | FANCA | c.3482C>T | p.(Thr1161Met) | 17.3 |
| Precursor B-cell acute lymphoblastic leukemia | FANCA | c.3391A>G | p.(Thr1131Ala) | 23.5 |
| Acute myeloid leukemia | FANCC | c.535C>T | p.(Arg179*) | 35.0 |
| Yolk sac tumor | FANCE | c.108delG | p.(Pro37Leufs*47) | 16.7 |
| Precursor B-cell acute lymphoblastic leukemia | FANCI | c.158-5A>G | p.(?) | 12.7 |
| Precursor T-cell acute lymphoblastic leukemia | FANCL | c.540+1G>A | p.(?) | 23.3 |
| Precursor B-cell acute lymphoblastic leukemia | FANCL | c.1007_1009delTAT | p.(Ile336_Cys337delinsSer) | 23.5 |
| Lymphoma | FANCL | c.1096_1099dupATTA | p.(Thr367Asnfs*13) | 35.0 |
| Acute myeloid leukemia1 | FANCM | c.681+1G>C | p.(?) | 25.9 |
| Rhabdomyosarcoma | FANCM | c.2156_2160delAACCA | p.(Lys719Serfs*15) | 36.0 |
| Plasmacytoid dendritic cell leukemia | NBN | c.156_157delTT | p.(Ser53Cysfs*8) | 25.6 |
| Wilms tumor | NBN | c.834dupA | p.(Gln279Serfs*6) | 37.0 |
| Precursor B-cell acute lymphoblastic leukemia | POLH | c.1600_1610delCA | p.(Gln534Glufs*11) | 40.0 |
| Precursor B-cell acute lymphoblastic leukemia | POLH | c.491-69_660+30del (deletion of exon 5) | p.(Glu164Glyfs*37) | – |
| Ganglioglioma | RECQL | c.1859C>G | p.(Ser620*) | 38.0 |
| Craniopharyngioma | RECQL | c.1859C>G | p.(Ser620*) | 38.0 |
| Precursor B-cell acute lymphoblastic leukemia | RECQL4 | c.3072delA | p.(Val1026Cysfs*18) | 21.7 |
| Lymphoma | RINT1 | c.88+3A>G | p.(?) | 15.4 |
| Glioma2 | TNFRSF13B | c.431C>G | p.(Ser144*) | 35.0 |
| Craniopharyngioma | WRAP53 | c.1192C>T | p.(Arg398Trp) | 34.0 |
| Precursor B-cell acute lymphoblastic leukemia | WRAP53 | c.1192C>T | p.(Arg398Trp) | 34.0 |
| Neurofibroma | XPC | c.1934delC | p.(Pro645Leufs*5) | 26.6 |
Three of the patients listed above also had a monoallelic pathogenic germline mutation (fam no. 13, 25 and 51).
Monoallelic variants in RECQL are pathogenic; however, their relationship to cancer is uncertain. Therefore, they are listed here.
1Same patient carrying the ADA and FANCM variants.
2Pathogenic variants (Romberg et al., 2013) may be inherited via an autosomal dominant or autosomal recessive. pattern. Based on the patient’s phenotype, this variant was considered inherited recessively.