Table 2.
Somatic mutations in the patient's tumor that were predicted to alter the protein sequence (single-nucleotide variants [SNVs]: missense, nonsense, affecting canonical splice site; indels: affecting coding exon, affecting canonical splice site), ordered by decreasing tumor allelic fraction of the alternate (nonreference) allele in the Illumina whole-exome sequencing (WES) data (ILMN)
| Tumor | Normal | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Alt allele fraction (%) | ILMN | PB | ILMN | PB | |||||||||||||||
| Gene symbol | Gene name | Gene ID | Chromosome | Mutation in DNA | Mutation in protein | Variant type | Predicted effect | dbSNP ID | ILMN | PB | Total reads | Alt allele reads | Total reads | Alt allele reads | Total reads | Alt alele reads | Total reads | Alt alele reads | Comments |
| AIG1 | Androgen- induced 1 | 51390 | 6 | NC_000006.11:g.143656205A>T | p.(Met239Leu) | SNV | missense_variant | 26 | 21* | 338 | 88 | 8,182* | 1,730* | 148 | 0 | 953 | 0 | Protein is predicted to change only in transcript isoform ENST00000275235 (intronic in all RefSeq and UniProt isoforms) | |
| ATP8A2 | ATPase phospholipid-transporting 8A2 | 51761 | 13 | NC_000013.10:g.26138117A>T | p.(Asp434Val), p.(Asp474Val) | SNV | missense_variant | 24 | 23* | 649 | 158 | 8,158* | 1,874* | 333 | 0 | 709 | 1 | ||
| USP8 | Ubiquitin-specific peptidase 8 | 9101 | 15 | NC_000015.9:g.50782647C>G | p.(Pro720Arg), p.(Pro614Arg) | SNV | missense_variant | rs672601311 | 22 | 20* | 333 | 72 | 7,044* | 1,417* | 141 | 0 | 694 | 0 | Pathogenic mechanism previously described (Ma et al. 2015; Reincke et al. 2015); ClinVar accession RCV000149420.1 |
| FRYL | FRY-like transcription coactivator | 285527 | 4 | NC_000004.11:g.48529993G>C | p.(Pro2379Ala) | SNV | missense_variant | 20 | 5 | 81 | 16 | 757 | 38 | 29 | 0 | 523 | 0 | ||
| PRPF18 | Pre-mRNA processing factor 18 | 8559 | 10 | NC_000010.10:g.13642266A>G | p.(Gln56Arg) | SNV | missense_variant | 19 | 15 | 471 | 89 | 1,288 | 190 | 169 | 0 | 1,090 | 1 | ||
| LGI3 | Leucine-rich repeat LGI family member 3 | 203190 | 8 | NC_000008.10:g.22006350G>C | p.(Gln324Glu) | SNV | missense_variant | 9 | 9 | 235 | 20 | 411 | 38 | 90 | 0 | 464 | 0 | ||
| MINK1 | Misshapen like kinase 1 | 50488 | 17 | NC_000017.10:g.4795451AGAG>A | p.(Arg671del) | deletion | inframe_deletion | 8 | 8 | 310 | 26 | 4,602 | 367 | 131 | 1 | 459 | 2 | ||
| PPFIBP2 | PPFIA binding protein 2 | 8495 | 11 | NC_000011.9:g.7661089C>A | p.(Leu455Met) | SNV | missense_variant | 7 | 2 | 154 | 11 | 518 | 9 | 120 | 0 | 563 | 0 | ||
| SLFN12 | Schlafen family member 12 | 55106 | 17 | NC_000017.10:g.33749940CA>C | p.(Leu36Argfs*6) | deletion | frameshift_variant | 6 | nd | 501 | 28 | nd | nd | 385 | 1 | nd | nd | Did not attempt PB validation | |
| PPEF1 | Protein phos phatase with EF-hand domain 1 | 5475 | X | NC_000023.10:g.18800487T>A | p.(Tyr243*) | SNV | stop_gained | 5 | 7 | 152 | 7 | 667 | 45 | 87 | 0 | 415 | 0 | Region undergoes copy loss based on CNA analysis; gene has an intronic somatic SNV (NC_000023.10:g.18752019G>A) with alt allele fraction of 17% | |
| MMP26 | Matrix metallo peptidase 26 | 56547 | 11 | NC_000011.9:g.5012679G>A | p.(Gly183Glu) | SNV | missense_variant | 4 | 3* | 185 | 8 | 6,025* | 188* | 117 | 0 | 148 | 0 | ||
| RASD1 | Ras-related dexameth asone induced 1 | 51655 | 17 | NC_000017.10:g.17399395T>A | p.(Lys34Met) | SNV | missense_variant | 3 | 3* | 406 | 12 | 32,529* | 923* | 175 | 0 | 1,790 | 1 | A different somatic mutation (p.K34R) has been observed at this position (COSMIC database mutation ID: COSM5385794) | |
| DCHS2 | Dachsous cad herin-related 2 | 54798 | 4 | NC_000004.11:g.155219314G>A | p.(Ser1596Leu) | SNV | missense_variant | rs747828053 | 3 | 20 | 557 | 19 | 576 | 118 | 430 | 0 | 588 | 0 | |
Read depth statistics are also shown for validation of mutations by targeted amplicon sequencing on PacBio (PB). Some amplicons yielded inconclusive evidence during the first PB sequencing run, and thus starred (*) data are from a second run where multiplexing was adjusted to yield higher depth for the given amplicons. Gene symbols and names are from HUGO Gene Nomenclature Committee (HGNC) (Gray et al. 2015) (retrieved 2016-05-25). Gene IDs are from the National Center for Biotechnology Information (NCBI) Gene (http://www.ncbi.nlm.nih.gov/gene, retrieved 2016-05-25). Mutations are given according to Human Genome Variation Society (HGVS) nomenclature (den Dunnen et al. 2016) version 15.11. Unless otherwise noted, amino acid numbering is from all canonical isoforms based on review of all Reference Sequencing Database (RefSeq) (Pruitt et al. 2014) and UniProtKB (The UniProt Consortium et al. 2015) isoforms at the given genomic location in the UCSC Genome Browser (Kent et al. 2002) (retrieved 2016-05-25). Predicted amino acid change and effect are from SnpEff version 4.0b (Cingolani et al. 2012) using Sequence Ontology terms (Cunningham et al. 2015). For ILMN data, read counts for total reads and reads supporting alternate allele are taken directly from the respective variant caller MuTect (Cibulskis et al. 2013) for SNVs and Varscan2 (Koboldt et al. 2012) for indels.
dbSNP, Database for Short Genetic Variations; COSMIC, Catalogue of Somatic Mutations in Cancer.