Table 2.
Overview of pathogenic/likely pathogenic variants associated with cancer predisposition identified in the patient cohort.
| Case; Diagnosis | Gene/ transcript | Chromosomal position in bp (hg19) | Nucleotide change; Amino acid change | Zygosity | Inheritance | Clinical signs | Associated syndrome |
|---|---|---|---|---|---|---|---|
| Case-68; B-ALL | PTPN11 ENST00000351677.2 | NC_000012.11:g.112915523A>G | c.922A>G; p.(Asn308Asp) | heterozygous | de novo | 2 | Noonan Syndrome |
| Case-76; GBM | MSH6 ENST00000234420.5 | NC_000002.11:g.48030698dup | c.3312dup; p.(Gly1105Trpfs*3) | heterozygous | de novo | None | Lynch Syndrome |
| Case-99; B-ALL | TP53 ENST00000269305.4 | NC_000017.10:g.7578263G>A | c.586C>T; p.(Arg196*) | heterozygous | de novo | 3 | Li Fraumeni Syndrome |
| Case-140; RMS | NF1 ENST00000358273.4 | NC_000017.10:g.29665160del | LRG_214t2:c.6819+3del; Splicing | heterozygous | de novo | 2 | NF type I |
| Case-7a; MB | MSH6 ENST00000234420.5 | NC_000002.11:g.48027547_48027549del | c.2426_2428del; p.(Val809del) | homozygous | Transmitted by mother + father | 2 | CMMRD |
| Case-10b; RMS | DICER1 ENST00000526495.1 | NC_000014.8:g.95570329dup | c.3405dup; p.(Gly1136Argfs*3) | heterozygous | Transmitted by father | 2 | DICER syndrome |
| Case-19; RMS | TP53 ENST00000269305.4 | NC_000017.10:g.7579558_7579596del | LRG_321t1:c.97-6_129del; Splicing | heterozygous | Transmitted by father | 2 | Li Fraumeni Syndrome |
| Case-31c; Plexus Ca | TP53 ENST00000269305.4 | NC_000017.10:g.7577548C>T | c.733G>A; p.(Gly245Ser) | heterozygous | Transmitted by father | 2 | Li Fraumeni Syndrome |
| Case-158; RMS | TP53 ENST00000269305.4 | NC_000017.10:g.7578393A>C | c.537T>G; p.(His179Gln) | heterozygous | Transmitted by father | 1 | Li Fraumeni Syndrome |
| Case-159d; T-ALL | ATM ENST00000278616.4 | NC_000011.9:g.108141874G>C | LRG_135t1:c.2921+1G > C; Splicing | homozygous | Transmitted by mother + father | 3 | Ataxia telangiectasia |
Diagnosis diagnosis of initial cancer disease, B-ALL B-cell acute lymphoblastic leukemia, Ca carcinoma, GBM glioblastoma, MB medulloblastoma, RMS rhabdomyosarcoma, T-ALL T-cell acute lymphoblastic leukemia, Clinical signs number of positive clinical signs indicating a cancer predisposition, NF type I neurofibromatosis type I, CMMRD constitutional mismatch repair deficiency syndrome
aVariant of Case-7 described in detail by Taeubner et al. [15].
bVariant of Case-10 described in detail in Fremerey et al. [13].
cVariant of Case-31 described in Brozou et al. [8].
dATM variant was identified during routine workup in an external diagnostic laboratory.