Table 2.
Enrichment of pathogenic variants in GB01, GB02, and GB03 somatic mutations. Gene, mutated gene. Variant, amino acid change or base substitution. Tumor (regions), tumor regions in which that mutation was detected. Genotype, heterozygous (het) or homozygous (hom) mutation. Type, type of genetic mutation. COSMIC, mutation already noted in the Catalogue of Somatic Mutations in Cancer (COSMIC). Described in CNS, variants that have already been described in brain tumor and annotated in COSMIC. Varsome, functional prediction of each variant classified using American College of Medical Genetics and Genomics (ACMG) rules.
| Gene | Variant | Tumor (Regions) | Genotype | Type | Cosmic | Described in CNS | VARSOME |
|---|---|---|---|---|---|---|---|
| APC | Gln163Lys | GB01-04 | het | Missense | Likely Pathogenic | ||
| ATM | Ser421Ter | GB01 (01, 02, 03, 04, 06, 07), GB02 (03, 07, 08) | het | Nonsense | COSM4165637 | Pathogenic | |
| ATR | Glu359Ter | GB02–05 | het | Nonsense | Pathogenic | ||
| Arg1951Ter | GB03–06 | het | Nonsense | COSM6933109 | Pathogenic | ||
| Gln264Ter | GB01–03 | het | Nonsense | Pathogenic | |||
| Trp2094Ter | GB01–04 | het | Nonsense | Pathogenic | |||
| BRAF | Arg271Ser | GB02–09 | het | Missense | Likely Pathogenic | ||
| Glu375Ter | GB01 (05) | het | Nonsense | COSM5702658 | Pathogenic | ||
| EGFR | Arg108Lys | GB02 (all) | het | Missense | COSM21683 | Y | Likely Pathogenic |
| Thr273Pro | GB02–02 | het | Missense | Likely Pathogenic | |||
| ERBB3 | Lys695ArgfsTer15 | GB01–04 | het | Frameshift | Pathogenic | ||
| Leu12Ter | GB01–01 | het | Nonsense | Pathogenic | |||
| c.2840-2A > G | GB01–02 | het | Splice Site | Pathogenic | |||
| KMT2D | Gln3370SerfsTer22 | GB03–03 | het | Frameshift | Pathogenic | ||
| Arg2830Ter | GB01–07 | het | Nonsense | COSM220674 | Y | Pathogenic | |
| MET | Thr230ArgfsTer33 | GB01–05 | het | Frameshift | Pathogenic | ||
| Asp449HisfsTer4 | GB01–08 | het | Frameshift | Pathogenic | |||
| MSH6 | Ala1302GlufsTer25 | GB01–09 | het | Frameshift | Pathogenic | ||
| Phe115LeufsTer34 | GB01–09 | het | Frameshift | Pathogenic | |||
| Phe1088SerfsTer2 | GB01–09, GB02 (05, 06), GB03 (08) | het | Frameshift | Pathogenic | |||
| MYC | Thr73Pro | GB01–01 | het | Missense | Likely Pathogenic | ||
| NOTCH1 | Val1229LeufsTer216 | GB01–03 | het | Frameshift | Pathogenic | ||
| His2275ProfsTer20 | GB01–08 | het | Frameshift | Pathogenic | |||
| Met2237CysfsTer11 | GB03–02 | het | Frameshift | Pathogenic | |||
| c.1556-2A > C | GB02 (02, 05) | het | Splice Site | Pathogenic | |||
| c.4587-2A > C | GB03 (08) | het | Splice Site | Pathogenic | |||
| Gly1339AlafsTer106 | GB03–06 | het | Splice Site | Pathogenic | |||
| PIK3CA | Ser1003Leu | GB01–01 | het | Missense | COSM5700983 | Likely Pathogenic | |
| Leu649Ile | GB01–03 | het | Missense | Likely Pathogenic | |||
| Ile391Lys | GB01–08 | het | Missense | Likely Pathogenic | |||
| Phe667Cys | GB02–01 | het | Missense | Likely Pathogenic | |||
| Cys838Trp | GB03–05 | het | Missense | Likely Pathogenic | |||
| Met1043Ile | GB03 (all) | het | Missense | COSM773 | Pathogenic | ||
| c.1540-1G > T | GB03–02 | het | Splice Site | Pathogenic | |||
| PTEN | Asp52Asn | GB01 (all) | het | Missense | COSM5059 | Likely Pathogenic | |
| Trp274Cys | GB02–06 | het | Missense | Likely Pathogenic | |||
| His272Gln | GB02–07 | het | Missense | Pathogenic | |||
| c.1027-2delA | GB01–07 | het | Splice Site | Pathogenic | |||
| RB1 | Leu337TrpfsTer12 | GB01–04 | het | Frameshift | Pathogenic | ||
| Leu683Pro | GB01–01 | het | Missense | Likely Pathogenic | |||
| Leu448Ile | GB01–02 | het | Missense | Likely Pathogenic | |||
| Leu400Met | GB01–04 | het | Missense | Likely Pathogenic | |||
| His483Asn | GB01–05 | het | Missense | Likely Pathogenic | |||
| Ile711Leu | GB02–07 | het | Missense | Likely Pathogenic | |||
| Glu465Ter | GB01–05 | het | Nonsense | COSM6936008 | Pathogenic | ||
| Tyr446Ter | GB02–02 | het | Nonsense | Pathogenic | |||
| Ser474Ile | GB01 (01–07) GB02 (03, 04, 08, 09) | het | Splice Site | COSM4807851 | Pathogenic | ||
| c.1421 + 1G > T | GB01 (02, 03, 05), GB02 (03) | het | Splice Site | Pathogenic | |||
| SF3B1 | Tyr623His | GB01–01 | het | Missense | Likely Pathogenic | ||
| Ile704Met | GB03–03 | het | Missense | Likely Pathogenic | |||
| Glu62Ter | GB03–03 | het | Nonsense | Pathogenic | |||
| Gln1252His | GB02–03 | het | Splice Site | Likely Pathogenic | |||
| Gln1252Ter | GB01–09 | het | Splice Site | Pathogenic | |||
| SOX2 | Arg57AlafsTer46 | GB01–08 | het | Frameshift | Pathogenic | ||
| Ala94Asp | GB01–08 | het | Missense | Likely Pathogenic | |||
| TERT | Ile1046Ter | GB01–09 | het | Frameshift | Pathogenic | ||
| c.2582 + 2T > G | GB02–08 | het | Splice Site | Pathogenic | |||
| TP53 | Tyr103Ser | GB02–09 | het | Missense | Likely Pathogenic | ||
| Gln144Ter | GB01–01 | het | Nonsense | Pathogenic |