Analysis of variants for LCC genes

Sean Davis

8/8/2019

Source: vignettes/lcc_variants.Rmd

Overview

Using the file available from /data/CCRBioinfo/projects/TargetOsteoManuscriptData/mutect_summary/TargetOsteoDNA.mutect.GATK_filter.tab:

I did the followign:

  • select unique SampleName, Chromosome, Start_Position, End_Position, Hugo_Symbol

Summary tables are below.

Results

Load variants and genes.

library(TargetOsteoAnalysis)
library(dplyr)
variants = variant_calls() # mutect calls as a tibble

And find unique variants for each of the LCC genes, regardless of sequencing technique used.

unique_vars = variants %>%
  dplyr::arrange(SampleName, Chromosome, Start_Position,
                 End_Position, Variant_Type, t_vaf) %>%
  dplyr::distinct(SampleName, Chromosome, Start_Position,
                  End_Position, Variant_Type, .keep_all=TRUE) %>%
  dplyr::rename(VariantAlleleFreq = t_vaf, HGVS = HGVSp_Short) %>%
  dplyr::select(SampleName, Chromosome, Start_Position,
                End_Position, Hugo_Symbol, Variant_Type,
                VariantAlleleFreq, HGVS, Transcript_ID,
                Consequence) %>%
  dplyr::filter(Hugo_Symbol %in% lcc_genes())

All unique variants for the LCC genes are:

SampleName Chromosome Start_Position End_Position Hugo_Symbol Variant_Type VariantAlleleFreq HGVS Transcript_ID Consequence
0A4HLD_Tumor chr17 7577106 7577106 TP53 SNP 0.8040000 p.P278S ENST00000269305 missense_variant
0A4HX8_Tumor chr17 7578461 7578461 TP53 SNP 0.8970000 p.V157F ENST00000269305 missense_variant
0A4I4E_Tumor chr13 49039206 49039206 RB1 SNP 0.8150000 p.Q762* ENST00000267163 stop_gained
0A4I4E_Tumor chr17 7578290 7578290 TP53 SNP 0.6720000 p.X187_splice ENST00000269305 splice_acceptor_variant
0A4I5B_Tumor chr17 7578257 7578257 TP53 SNP 0.5930000 p.E198* ENST00000269305 stop_gained
0A4I6O_Tumor chr17 7578532 7578532 TP53 SNP 0.5430000 p.M133K ENST00000269305 missense_variant
0A4I9K_Tumor chr17 7577097 7577097 TP53 SNP 0.6730000 p.D281N ENST00000269305 missense_variant
NAAECZ_Tumor chr17 7577142 7577142 TP53 SNP 0.5000000 p.G266R ENST00000269305 missense_variant
NAAEDB_Tumor chr17 7578192 7578192 TP53 DEL 0.7740000 p.Y220Mfs*27 ENST00000269305 frameshift_variant
NAAEDG_Tumor chr17 7577498 7577498 TP53 SNP 0.5830000 p.X261_splice ENST00000269305 splice_donor_variant
NAAGJP_Tumor chr17 7577094 7577094 TP53 SNP 0.1279621 p.R282W ENST00000269305 missense_variant
NAAGJP_Tumor chrX 76938407 76938407 ATRX SNP 0.1140000 p.R781* ENST00000373344 stop_gained
NAAGJZ_Tumor chrX 76937963 76937963 ATRX SNP 0.3676471 p.Q929E ENST00000373344 missense_variant
NAAGKM_Tumor chr17 7579373 7579373 TP53 SNP 0.6360000 p.G105V ENST00000269305 missense_variant
NAAHBI_Tumor chr17 7577018 7577018 TP53 SNP 0.8250000 p.X307_splice ENST00000269305 splice_donor_variant
NAAHBK_Tumor chr17 7577114 7577114 TP53 SNP 0.1890000 p.C275Y ENST00000269305 missense_variant
NAAHBU_RecurrentTumor chr17 7579358 7579358 TP53 SNP 0.8700000 p.R110L ENST00000269305 missense_variant
NAAHBU_RecurrentTumor chrX 76939918 76939918 ATRX SNP 0.1910000 p.V277D ENST00000373344 missense_variant
NAAHBU_Tumor chr17 7579358 7579358 TP53 SNP 0.4740000 p.R110L ENST00000269305 missense_variant
NAAHBY_RecurrentTumor chr17 7578525 7578525 TP53 SNP 0.4120000 p.C135W ENST00000269305 missense_variant
NAAHBY_Tumor chr17 7578525 7578525 TP53 SNP 0.5170000 p.C135W ENST00000269305 missense_variant
NAAHBZ_Tumor chr17 7577097 7577097 TP53 SNP 0.5530000 p.D281Y ENST00000269305 missense_variant
NAAHCF_Tumor chr17 7578382 7578382 TP53 SNP 0.5820000 p.S183* ENST00000269305 stop_gained
NAAHCH_Tumor chr17 7577539 7577539 TP53 SNP 0.6630000 p.R248W ENST00000269305 missense_variant
NAAHCJ_RecurrentTumor chr17 7579416 7579446 TP53 DEL 0.7140000 p.T81Gfs*32 ENST00000269305 frameshift_variant
NAAHCJ_Tumor chr17 7579416 7579446 TP53 DEL 0.7860000 p.T81Gfs*32 ENST00000269305 frameshift_variant
NAAHCR_Tumor chr17 7578545 7578545 TP53 DEL 0.5660000 p.A129Pfs*41 ENST00000269305 frameshift_variant
NAAHDF_Tumor chr10 89692911 89692911 PTEN SNP 0.1150000 p.G132D ENST00000371953 missense_variant
NAAHDL_Tumor chr17 7577108 7577108 TP53 SNP 0.3650000 p.C277F ENST00000269305 missense_variant
NAAIBU_Tumor chr13 48881488 48881489 RB1 INS 0.2777778 p.A74Efs*4 ENST00000267163 frameshift_variant
NAAIBW_Tumor chr10 89685296 89685296 PTEN SNP 0.5142857 p.H64P ENST00000371953 missense_variant
NAASJI_Tumor chr17 7579310 7579310 TP53 SNP 0.4838710 p.X125_splice ENST00000269305 splice_donor_variant
NAAWEX_Tumor chr17 7577121 7577121 TP53 SNP 0.7610000 p.R273C ENST00000269305 missense_variant
NAAWGR_Tumor chrX 76940042 76940042 ATRX DEL 0.6770000 p.H236Ifs*21 ENST00000373344 frameshift_variant
PAIXFY_Tumor chr13 48921987 48921987 RB1 DEL 0.7220000 p.Q176Hfs*10 ENST00000267163 frameshift_variant
PAKUZU_Tumor chr13 49039169 49039169 RB1 SNP 0.5590000 p.Y749* ENST00000267163 stop_gained
PAKXLD_Tumor chr17 7577120 7577120 TP53 SNP 0.5910000 p.R273H ENST00000269305 missense_variant
PAKZZK_Tumor chr17 7577094 7577094 TP53 SNP 0.6600000 p.R282W ENST00000269305 missense_variant
PAMHLF_Tumor chr17 7578190 7578190 TP53 SNP 0.8330000 p.Y220C ENST00000269305 missense_variant
PAMJXS_Tumor chr17 7577114 7577114 TP53 SNP 0.7250000 p.C275Y ENST00000269305 missense_variant
PAMRHD_Tumor chr13 49037915 49037917 RB1 DEL 0.5860000 p.L719del ENST00000267163 inframe_deletion
PAMYYJ_Tumor chr13 49027153 49027154 RB1 INS 0.6110000 p.K574Ifs*11 ENST00000267163 frameshift_variant
PAMYYJ_Tumor chrX 76937383 76937383 ATRX DEL 0.6000000 p.C1122Lfs*8 ENST00000373344 frameshift_variant
PANGCY_Tumor chr22 30050681 30050682 NF2 INS 0.0940000 p.L163Ffs*40 ENST00000338641 frameshift_variant
PANMIG_Tumor chr13 49027128 49027128 RB1 SNP 0.7710000 p.X566_splice ENST00000267163 splice_acceptor_variant
PANMIG_Tumor chrX 76855051 76855051 ATRX SNP 0.9160000 p.X1929_splice ENST00000373344 splice_acceptor_variant
PAPVYW_Tumor chr17 7577120 7577120 TP53 SNP 0.3750000 p.R273H ENST00000269305 missense_variant
PARDAX_Tumor chr13 48955550 48955550 RB1 SNP 0.7500000 p.R556* ENST00000267163 stop_gained
PARDAX_Tumor chr17 7578203 7578203 TP53 SNP 0.7880000 p.V216M ENST00000269305 missense_variant
PASEFS_Tumor chr17 7576855 7576855 TP53 SNP 0.9920000 p.Q331* ENST00000269305 stop_gained,splice_region_variant
PASEFS_Tumor chrX 76938593 76938594 ATRX INS 0.9680000 p.S719Ifs*2 ENST00000373344 frameshift_variant
PASKZZ_Tumor chr17 7578475 7578475 TP53 DEL 0.6500000 p.P152Rfs*18 ENST00000269305 frameshift_variant
PASNZV_Tumor chr13 48955538 48955538 RB1 SNP 0.6260000 p.R552* ENST00000267163 stop_gained
PASNZV_Tumor chr17 7579324 7579325 TP53 INS 0.6680000 p.V122Sfs*3 ENST00000269305 frameshift_variant
PASSLM_Tumor chr13 48953743 48953743 RB1 SNP 0.8150000 p.G449V ENST00000267163 missense_variant
PASSLM_Tumor chr17 7577498 7577498 TP53 SNP 0.9440000 p.X261_splice ENST00000269305 splice_donor_variant
PASSLM_Tumor chrX 76937879 76937880 ATRX INS 0.9430000 p.V957Sfs*7 ENST00000373344 frameshift_variant
PATMXR_Tumor chrX 76891541 76891541 ATRX SNP 0.4184100 p.E1522K ENST00000373344 missense_variant
PATPBS_Tumor chr17 7577094 7577094 TP53 SNP 0.5640000 p.R282W ENST00000269305 missense_variant
PATUXZ_Tumor chrX 76874323 76874323 ATRX SNP 0.7260000 p.M1800K ENST00000373344 missense_variant
PAVDSN_Tumor chr17 7577545 7577545 TP53 SNP 0.8560000 p.M246V ENST00000269305 missense_variant
PAVLIB_Tumor chr17 7577142 7577142 TP53 SNP 0.1160000 p.G266R ENST00000269305 missense_variant
PAVXDP_Tumor chr17 7578532 7578532 TP53 SNP 0.7000000 p.M133K ENST00000269305 missense_variant

Removing recurrent tumors:

SampleName Chromosome Start_Position End_Position Hugo_Symbol Variant_Type VariantAlleleFreq HGVS Transcript_ID Consequence
0A4HLD_Tumor chr17 7577106 7577106 TP53 SNP 0.8040000 p.P278S ENST00000269305 missense_variant
0A4HX8_Tumor chr17 7578461 7578461 TP53 SNP 0.8970000 p.V157F ENST00000269305 missense_variant
0A4I4E_Tumor chr13 49039206 49039206 RB1 SNP 0.8150000 p.Q762* ENST00000267163 stop_gained
0A4I4E_Tumor chr17 7578290 7578290 TP53 SNP 0.6720000 p.X187_splice ENST00000269305 splice_acceptor_variant
0A4I5B_Tumor chr17 7578257 7578257 TP53 SNP 0.5930000 p.E198* ENST00000269305 stop_gained
0A4I6O_Tumor chr17 7578532 7578532 TP53 SNP 0.5430000 p.M133K ENST00000269305 missense_variant
0A4I9K_Tumor chr17 7577097 7577097 TP53 SNP 0.6730000 p.D281N ENST00000269305 missense_variant
NAAECZ_Tumor chr17 7577142 7577142 TP53 SNP 0.5000000 p.G266R ENST00000269305 missense_variant
NAAEDB_Tumor chr17 7578192 7578192 TP53 DEL 0.7740000 p.Y220Mfs*27 ENST00000269305 frameshift_variant
NAAEDG_Tumor chr17 7577498 7577498 TP53 SNP 0.5830000 p.X261_splice ENST00000269305 splice_donor_variant
NAAGJP_Tumor chr17 7577094 7577094 TP53 SNP 0.1279621 p.R282W ENST00000269305 missense_variant
NAAGJP_Tumor chrX 76938407 76938407 ATRX SNP 0.1140000 p.R781* ENST00000373344 stop_gained
NAAGJZ_Tumor chrX 76937963 76937963 ATRX SNP 0.3676471 p.Q929E ENST00000373344 missense_variant
NAAGKM_Tumor chr17 7579373 7579373 TP53 SNP 0.6360000 p.G105V ENST00000269305 missense_variant
NAAHBI_Tumor chr17 7577018 7577018 TP53 SNP 0.8250000 p.X307_splice ENST00000269305 splice_donor_variant
NAAHBK_Tumor chr17 7577114 7577114 TP53 SNP 0.1890000 p.C275Y ENST00000269305 missense_variant
NAAHBU_Tumor chr17 7579358 7579358 TP53 SNP 0.4740000 p.R110L ENST00000269305 missense_variant
NAAHBY_Tumor chr17 7578525 7578525 TP53 SNP 0.5170000 p.C135W ENST00000269305 missense_variant
NAAHBZ_Tumor chr17 7577097 7577097 TP53 SNP 0.5530000 p.D281Y ENST00000269305 missense_variant
NAAHCF_Tumor chr17 7578382 7578382 TP53 SNP 0.5820000 p.S183* ENST00000269305 stop_gained
NAAHCH_Tumor chr17 7577539 7577539 TP53 SNP 0.6630000 p.R248W ENST00000269305 missense_variant
NAAHCJ_Tumor chr17 7579416 7579446 TP53 DEL 0.7860000 p.T81Gfs*32 ENST00000269305 frameshift_variant
NAAHCR_Tumor chr17 7578545 7578545 TP53 DEL 0.5660000 p.A129Pfs*41 ENST00000269305 frameshift_variant
NAAHDF_Tumor chr10 89692911 89692911 PTEN SNP 0.1150000 p.G132D ENST00000371953 missense_variant
NAAHDL_Tumor chr17 7577108 7577108 TP53 SNP 0.3650000 p.C277F ENST00000269305 missense_variant
NAAIBU_Tumor chr13 48881488 48881489 RB1 INS 0.2777778 p.A74Efs*4 ENST00000267163 frameshift_variant
NAAIBW_Tumor chr10 89685296 89685296 PTEN SNP 0.5142857 p.H64P ENST00000371953 missense_variant
NAASJI_Tumor chr17 7579310 7579310 TP53 SNP 0.4838710 p.X125_splice ENST00000269305 splice_donor_variant
NAAWEX_Tumor chr17 7577121 7577121 TP53 SNP 0.7610000 p.R273C ENST00000269305 missense_variant
NAAWGR_Tumor chrX 76940042 76940042 ATRX DEL 0.6770000 p.H236Ifs*21 ENST00000373344 frameshift_variant
PAIXFY_Tumor chr13 48921987 48921987 RB1 DEL 0.7220000 p.Q176Hfs*10 ENST00000267163 frameshift_variant
PAKUZU_Tumor chr13 49039169 49039169 RB1 SNP 0.5590000 p.Y749* ENST00000267163 stop_gained
PAKXLD_Tumor chr17 7577120 7577120 TP53 SNP 0.5910000 p.R273H ENST00000269305 missense_variant
PAKZZK_Tumor chr17 7577094 7577094 TP53 SNP 0.6600000 p.R282W ENST00000269305 missense_variant
PAMHLF_Tumor chr17 7578190 7578190 TP53 SNP 0.8330000 p.Y220C ENST00000269305 missense_variant
PAMJXS_Tumor chr17 7577114 7577114 TP53 SNP 0.7250000 p.C275Y ENST00000269305 missense_variant
PAMRHD_Tumor chr13 49037915 49037917 RB1 DEL 0.5860000 p.L719del ENST00000267163 inframe_deletion
PAMYYJ_Tumor chr13 49027153 49027154 RB1 INS 0.6110000 p.K574Ifs*11 ENST00000267163 frameshift_variant
PAMYYJ_Tumor chrX 76937383 76937383 ATRX DEL 0.6000000 p.C1122Lfs*8 ENST00000373344 frameshift_variant
PANGCY_Tumor chr22 30050681 30050682 NF2 INS 0.0940000 p.L163Ffs*40 ENST00000338641 frameshift_variant
PANMIG_Tumor chr13 49027128 49027128 RB1 SNP 0.7710000 p.X566_splice ENST00000267163 splice_acceptor_variant
PANMIG_Tumor chrX 76855051 76855051 ATRX SNP 0.9160000 p.X1929_splice ENST00000373344 splice_acceptor_variant
PAPVYW_Tumor chr17 7577120 7577120 TP53 SNP 0.3750000 p.R273H ENST00000269305 missense_variant
PARDAX_Tumor chr13 48955550 48955550 RB1 SNP 0.7500000 p.R556* ENST00000267163 stop_gained
PARDAX_Tumor chr17 7578203 7578203 TP53 SNP 0.7880000 p.V216M ENST00000269305 missense_variant
PASEFS_Tumor chr17 7576855 7576855 TP53 SNP 0.9920000 p.Q331* ENST00000269305 stop_gained,splice_region_variant
PASEFS_Tumor chrX 76938593 76938594 ATRX INS 0.9680000 p.S719Ifs*2 ENST00000373344 frameshift_variant
PASKZZ_Tumor chr17 7578475 7578475 TP53 DEL 0.6500000 p.P152Rfs*18 ENST00000269305 frameshift_variant
PASNZV_Tumor chr13 48955538 48955538 RB1 SNP 0.6260000 p.R552* ENST00000267163 stop_gained
PASNZV_Tumor chr17 7579324 7579325 TP53 INS 0.6680000 p.V122Sfs*3 ENST00000269305 frameshift_variant
PASSLM_Tumor chr13 48953743 48953743 RB1 SNP 0.8150000 p.G449V ENST00000267163 missense_variant
PASSLM_Tumor chr17 7577498 7577498 TP53 SNP 0.9440000 p.X261_splice ENST00000269305 splice_donor_variant
PASSLM_Tumor chrX 76937879 76937880 ATRX INS 0.9430000 p.V957Sfs*7 ENST00000373344 frameshift_variant
PATMXR_Tumor chrX 76891541 76891541 ATRX SNP 0.4184100 p.E1522K ENST00000373344 missense_variant
PATPBS_Tumor chr17 7577094 7577094 TP53 SNP 0.5640000 p.R282W ENST00000269305 missense_variant
PATUXZ_Tumor chrX 76874323 76874323 ATRX SNP 0.7260000 p.M1800K ENST00000373344 missense_variant
PAVDSN_Tumor chr17 7577545 7577545 TP53 SNP 0.8560000 p.M246V ENST00000269305 missense_variant
PAVLIB_Tumor chr17 7577142 7577142 TP53 SNP 0.1160000 p.G266R ENST00000269305 missense_variant
PAVXDP_Tumor chr17 7578532 7578532 TP53 SNP 0.7000000 p.M133K ENST00000269305 missense_variant

Gene counts (counting each gene only once per sample) are:

unique_gene_samples = unique_vars %>%
  dplyr::filter(!grepl('recurrent', SampleName, ignore.case = TRUE)) %>%
  dplyr::select(SampleName, Hugo_Symbol) %>%
  unique()
sort(table(unique_gene_samples$Hugo_Symbol))
## 
##  NF2 PTEN ATRX  RB1 TP53 
##    1    2    9   10   37

Exported data

readr::write_lines(paste('# Protein-altering somatic variants in any of the genes ', paste(lcc_genes(), collapse=", ")), '/tmp/unique_vars_LCC_mutect.csv')
readr::write_csv(unique_vars, '/tmp/unique_vars_LCC_mutect.csv', append=TRUE, col_names = TRUE)