Output files
PCGR generates multiple output files, including interactive HTML reports and pure variant annotation files (tab-separated values (TSV)).
HTML report - dashboard
An interactive and tier-structured HTML report (dashboard-like) that shows the most relevant findings in the query cancer genome has the following naming convention:
-
<sample_id>.pcgr_acmg.<genome_assembly>.flexdb.html- The sample_id is provided as input by the user, and reflects a unique identifier of the tumor-normal sample pair to be analyzed.
HTML report - rmarkdown
An interactive and tier-structured HTML report that shows the most relevant findings in the query cancer genome has the following naming convention:
-
<sample_id>.pcgr_acmg.<genome_assembly>.html- The sample_id is provided as input by the user, and reflects a unique identifier of the tumor-normal sample pair to be analyzed.
The report is structured in seven main sections, described in more detail below:
-
Report and query settings
- Lists key configurations provided by user
-
Main results
- Nine value boxes that highlight the main properties of the tumor
sample:
- Tumor purity - as provided by the user
- Tumor ploidy - as provided by the user
- Mutational signatures - two most prevalent signatures (other than aging)
- Tier 1 variants (top four)
- Tier 2 variants (top four)
- Tumor mutational burden (TMB)
- Microsatellite instability (MSI) status
- Somatic copy number aberrations of clinical significance
- Kataegis events
- Nine value boxes that highlight the main properties of the tumor
sample:
-
Somatic SNVs/InDels
-
Tumor mutational burden (TMB)
- given a coding target region size specified by the user (ideally the callable target size), an estimate of the mutational burden is provided
- The estimated TMB is shown in the context of TMB distributions from different primary sites in TCGA
-
Tier & variant statistics
- indicate total variant numbers across variant types, coding types and tiers
-
Global distribution - allelic support
- distribution (histogram) of variant allelic support for somatic variants (will only be present in the report if specific fields in input VCF is defined and specified by the user)
-
Global variant browser
- permits exploration of the whole SNV/InDel dataset by filtering along several dimensions (call confidence, variant sequencing depth/support, variant consequence etc.)
-
Tier tables
- Variants are organized into five (tier 1-4 + noncoding) interactive datatables) according to clinical utility
- Contents of the tier tables are outlined below
-
Tumor mutational burden (TMB)
-
Somatic CNAs
-
Segments - amplifications and homozygous deletions
- Based on user-defined/default log-ratio thresholds of gains/losses, the whole CNA dataset can be navigated further through filters:
- cytoband
- type of CNA event - focal (less than 25% of chromosome arm affected) or broad
- log ratio
-
Proto-oncogenes subject to copy number amplifications
- Datatable listing known proto-oncogenes covered by user-defined/default amplifications and potential targeted therapies
-
Tumor suppressor genes subject to homozygous deletions
- Datatable listing known tumor suppressor genes covered by user-defined/default losses and potential targeted therapies
- Other drug targets subject to copy number aplifications
-
Copy number aberrations as biomarkers for prognosis, diagnosis,
and drug response (both of strong significance and
potential significance)
- Interactive data table where the user can navigate aberrations acting as biomarkers across therapeutic contexts, tumor subtypes, evidence levels etc
-
Segments - amplifications and homozygous deletions
-
MSI status
- Indicates predicted microsatellite stability from the somatic mutation profile and supporting evidence (details of the underlying MSI statistical classifier can be found here)
- The MSI classifier was trained on TCGA exome samples.
-
Mutational signatures
- Estimation of relative contribution of 67 known mutational signatures in tumor sample (using MutationalPatterns as the underlying framework)
- Datatable with signatures and proposed underlying etiologies
-
Kataegis events
- Detection of potential kataegis events using the algorithm outlined in the Kataegis Portal
-
Germline findings
- Main findings from CPSR report
-
Clinial trials
- Interactive table with annotated, molecularly targeted clinical trials from clinicaltrials.gov in the relevant tumor type
-
Documentation
- Annotation resources - software, databases and tools with version information
- Report content
- References - supporting scientific literature (key report elements)
Interactive datatables
The interactive datatables contain a number of hyperlinked annotations similar to those defined for the annotated VCF file, including the following:
| Annotation | Description |
|---|---|
SYMBOL |
Gene symbol (Entrez/NCBI) |
PROTEIN_CHANGE |
Amino acid change (VEP) |
CANCER_TYPE |
Biomarker (tier 1/2): associated cancer type |
EVIDENCE_LEVEL |
Biomarker (tier 1/2): evidence level (A,B,C,D,E) |
CLINICAL_SIGNIFICANCE |
Biomarker (tier 1/2): drug sensitivity, poor/better outcome etc |
EVIDENCE_TYPE |
Biomarker (tier 1/2): predictive/diagnostic/therapeutic |
DISEASE_ONTOLOGY_ID |
Biomarker (tier 1/2): associated cancer type (Disease Ontology) |
EVIDENCE_DIRECTION |
Biomarker (tier 1/2): supports/does not support |
DESCRIPTION |
Biomarker (tier 1/2): description |
VARIANT_ORIGIN |
Biomarker (tier 1/2): variant origin (germline/somatic) |
BIOMARKER_MAPPING |
Biomarker (tier 1/2): accuracy of genomic mapping (exact,codon,exon) |
CITATIO |
Biomarker (tier 1/2): supporting literature |
THERAPEUTIC_CONTEXT |
Biomarker (tier 1/2): associated drugs |
RATING |
Biomarker (tier 1/2): trust rating from 1 to 5 (CIVIC) |
GENE_NAME |
gene name description (Entrez/NCBI) |
PROTEIN_DOMAIN |
PFAM protein domain |
PROTEIN_FEATURE |
UniProt feature overlapping variant site |
CDS_CHANGE |
Coding sequence change |
MUTATION_HOTSPOT |
Known cancer mutation hotspot |
MUTATION_HOTSPOT_CANCERTYPE |
Hotspot-associated cancer types |
TCGA_FREQUENCY |
Frequency of variant in TCGA cohorts |
ICGC_PCAWG_OCCURRENCE |
Frequency of variant in ICGC-PCAWG cohorts |
DOCM_LITERATURE |
Literature links - DoCM |
DOCM_DISEASE |
Associated diseases - DoCM |
OPENTARGETS_RANK |
Strength (max across all phenotypes) of phenotype association according to the Open Targets Platform |
OPENTARGETS_ASSOCIATIONS |
Phenotype associations with the gene retrieved from the Open Targets Platform |
INTOGEN_DRIVER_MUT |
predicted driver mutation - IntOGen |
CONSEQUENCE |
VEP consequence (primary transcript) |
HGVSc |
from VEP |
HGVSp |
from VEP |
NCBI_REFSEQ |
Transcript accession ID(s) (NCBI RefSeq) |
ONCOGENE |
Predicted as proto-oncogene from CancerMine/NCG |
CANCERGENE_SUPPORT |
Links to underlying publications (CancerMine) that support oncogenic/tumor suppressive role of gene |
TUMOR_SUPPRESSOR |
Predicted as tumor suppressor gene from CancerMine/NCG |
PREDICTED_EFFECT |
Effect predictions from dbNSFP |
VEP_ALL_CSQ |
All VEP transcript block consequences |
DBSNP |
dbSNP rsID |
COSMIC |
Cosmic mutation IDs |
CLINVAR |
ClinVar variant origin and associated phenotypes |
CANCER_ASSOCIATIONS |
Gene-associated cancer types from DisGenet |
TARGETED_DRUGS |
Targeted drugs from Open Targets Platform /ChEMBL |
KEGG_PATHWAY |
Gene-associated pathways from KEGG |
CALL_CONFIDENCE |
Variant confidence (as set by user in input VCF) |
DP_TUMOR |
Variant sequencing depth in tumor (as set by user in input VCF) |
AF_TUMOR |
Variant allelic fraction in tumor (as set by user in input VCF) |
DP_CONTROL |
Variant sequencing depth in control sample (as set by user in input VCF) |
AF_CONTROL |
Variant allelic fraction in control sample (as set by user in input VCF) |
GENOMIC_CHANGE |
Variant ID |
GENOME_VERSION |
Genome assembly |
JSON
A compressed JSON file that stores all the essential content of the report is provided.
This file will easen the process of extracting particular parts of the report for further analysis or integration with other workflows. The JSON contains two main objects, metadata and content, where the former contains information about the settings, data versions, and the latter contains the various sections of the report.
SNVs/InDels
1. Variant call format - VCF
A VCF file containing annotated, somatic calls (single nucleotide variants and insertion/deletions) is generated with the following naming convention:
-
<sample_id>.pcgr_acmg.<genome_assembly>.vcf.gz- The sample_id is provided as input by the user, and reflects a unique identifier of the tumor-normal sample pair to be analyzed. Following common standards, the annotated VCF file is compressed with bgzip and indexed with tabix. Below follows a description of all annotations/tags present in the VCF INFO column after processing with the PCGR annotation pipeline:
VEP consequence annotations
| Tag | Description |
|---|---|
CSQ |
Complete consequence annotations from VEP. Format (separated by a
|): Allele, Consequence,
IMPACT, SYMBOL, Gene,
Feature_type, Feature, BIOTYPE,
EXON, INTRON, HGVSc,
HGVSp, cDNA_position,
CDS_position, Protein_position,
Amino_acids, Codons,
Existing_variation, ALLELE_NUM,
DISTANCE, STRAND, FLAGS,
PICK, VARIANT_CLASS,
SYMBOL_SOURCE, HGNC_ID,
CANONICAL, MANE_SELECT,
MANE_PLUS_CLINICAL, TSL, APPRIS,
CCDS, ENSP, SWISSPROT,
TREMBL, UNIPARC, UNIPROT_ISOFORM,
RefSeq, DOMAINS, HGVS_OFFSET,
AF, AFR_AF, AMR_AF,
EAS_AF, EUR_AF, SAS_AF,
gnomAD_AF, gnomAD_AFR_AF,
gnomAD_AMR_AF, gnomAD_ASJ_AF,
gnomAD_EAS_AF, gnomAD_FIN_AF,
gnomAD_NFE_AF, gnomAD_OTH_AF,
gnomAD_SAS_AF, CLIN_SIG, SOMATIC,
PHENO, CHECK_REF, MOTIF_NAME,
MOTIF_POS, HIGH_INF_POS,
MOTIF_SCORE_CHANGE, TRANSCRIPTION_FACTORS,
NearestExonJB
|
Consequence |
Impact modifier for the consequence type (picked by VEP’s
--flag_pick_allele option) |
Gene |
Ensembl stable ID of affected gene (picked by VEP’s
--flag_pick_allele option) |
Feature_type |
Type of feature. Currently one of Transcript, RegulatoryFeature,
MotifFeature (picked by VEP’s --flag_pick_allele
option) |
Feature |
Ensembl stable ID of feature (picked by VEP’s
--flag_pick_allele option) |
cDNA_position |
Relative position of base pair in cDNA sequence (picked by VEP’s
--flag_pick_allele option) |
CDS_position |
Relative position of base pair in coding sequence (picked by VEP’s
--flag_pick_allele option) |
CDS_CHANGE |
Coding, transcript-specific sequence annotation (picked by VEP’s
--flag_pick_allele option) |
AMINO_ACID_START |
Protein position indicating absolute start of amino acid altered
(fetched from Protein_position) |
AMINO_ACID_END |
Protein position indicating absolute end of amino acid altered
(fetched from Protein_position) |
Protein_position |
Relative position of amino acid in protein (picked by VEP’s
--flag_pick_allele option) |
Amino_acids |
Only given if the variant affects the protein-coding sequence
(picked by VEP’s --flag_pick_allele option) |
Codons |
The alternative codons with the variant base in upper case (picked
by VEP’s --flag_pick_allele option) |
IMPACT |
Impact modifier for the consequence type (picked by VEP’s
--flag_pick_allele option) |
VARIANT_CLASS |
Sequence Ontology variant class (picked by VEP’s
--flag_pick_allele option) |
SYMBOL |
Gene symbol (picked by VEP’s --flag_pick_allele
option) |
SYMBOL_ENTREZ |
Official gene symbol as provided by NCBI’s Entrez gene |
SYMBOL_SOURCE |
The source of the gene symbol (picked by VEP’s
--flag_pick_allele option) |
STRAND |
The DNA strand (1 or -1) on which the transcript/feature lies
(picked by VEP’s --flag_pick_allele option) |
ENSP |
The Ensembl protein identifier of the affected transcript (picked by
VEP’s --flag_pick_allele option) |
FLAGS |
Transcript quality flags: cds_start_NF: CDS 5’,
incomplete cds_end_NF: CDS 3’ incomplete (picked by VEP’s
--flag_pick_allele option) |
SWISSPROT |
Best match UniProtKB/Swiss-Prot accession of protein product (picked
by VEP’s --flag_pick_allele option) |
TREMBL |
Best match UniProtKB/TrEMBL accession of protein product (picked by
VEP’s --flag_pick_allele option) |
UNIPARC |
Best match UniParc accession of protein product (picked by VEP’s
--flag_pick_allele option) |
HGVSc |
The HGVS coding sequence name (picked by VEP’s
--flag_pick_allele option) |
HGVSp |
The HGVS protein sequence name (picked by VEP’s
--flag_pick_allele option) |
HGVSp_short |
The HGVS protein sequence name, short version (picked by VEP’s
--flag_pick_allele option) |
HGVS_OFFSET |
Indicates by how many bases the HGVS notations for this variant have
been shifted (picked by VEP’s --flag_pick_allele
option) |
NearestExonJB |
VEP plugin that finds nearest exon junction for a coding sequence variant. Format: Ensembl exon identifier+distanceto exon boundary+boundary type(start/end)+exon length |
MOTIF_NAME |
The source and identifier of a transcription factor binding profile
aligned at this position (picked by VEP’s
--flag_pick_allele option) |
MOTIF_POS |
The relative position of the variation in the aligned TFBP (picked
by VEP’s --flag_pick_allele option) |
HIGH_INF_POS |
A flag indicating if the variant falls in a high information
position of a transcription factor binding profile (TFBP) (picked by
VEP’s --flag_pick_allele option) |
MOTIF_SCORE_CHANGE |
The difference in motif score of the reference and variant sequences
for the TFBP (picked by VEP’s --flag_pick_allele
option) |
CELL_TYPE |
List of cell types and classifications for regulatory feature
(picked by VEP’s --flag_pick_allele option) |
CANONICAL |
A flag indicating if the transcript is denoted as the canonical
transcript for this gene (picked by VEP’s
--flag_pick_allele option) |
CCDS |
The CCDS identifier for this transcript, where applicable (picked by
VEP’s --flag_pick_allele option) |
INTRON |
The intron number (out of total number) (picked by VEP’s
--flag_pick_allele option) |
EXON |
The exon number (out of total number) (picked by VEP’s
--flag_pick_allele option) |
LAST_EXON |
Logical indicator for last exon of transcript (picked by VEP’s
--flag_pick_allele option) |
LAST_INTRON |
Logical indicator for last intron of transcript (picked by VEP’s
--flag_pick_allele option) |
INTRON_POSITION |
Relative position of intron variant to nearest exon/intron junction (NearestExonJB VEP plugin) |
EXON_POSITION |
Relative position of exon variant to nearest intron/exon junction (NearestExonJB VEP plugin) |
DISTANCE |
Shortest distance from variant to transcript (picked by VEP’s
--flag_pick_allele option) |
BIOTYPE |
Biotype of transcript or regulatory feature (picked by VEP’s
--flag_pick_allele option) |
TSL |
Transcript support level (picked by VEP’s
--flag_pick_allele option)> |
PUBMED |
PubMed ID(s) of publications that cite existing variant - VEP |
PHENO |
Indicates if existing variant is associated with a phenotype, disease or trait - VEP |
GENE_PHENO |
Indicates if overlapped gene is associated with a phenotype, disease or trait - VEP |
ALLELE_NUM |
Allele number from input; 0 is reference, 1 is first alternate etc - VEP |
REFSEQ_MATCH |
The RefSeq transcript match status; contains a number of flags
indicating whether this RefSeq transcript matches the underlying
reference sequence and/or an Ensembl transcript (picked by VEP’s
--flag_pick_allele option) |
PICK |
Indicates if this block of consequence data was picked by VEP’s
--flag_pick_allele option |
VEP_ALL_CONSEQUENCE |
All transcript consequences
(Consequence:SYMBOL:Feature_type:Feature:BIOTYPE) -
VEP |
EXONIC_STATUS |
Indicates if variant consequence type is ‘exonic’ or ‘nonexonic’. We
here define ‘exonic’ as any variant with either of the following
consequences: stop_gained / stop_lost,
start_lost, frameshift_variant,
missense_variant, splice_donor_variant,
splice_acceptor_variant,
inframe_insertion / inframe_deletion,
synonymous_variant, protein_altering
|
CODING_STATUS |
Indicates if primary variant consequence type is ‘coding’ or ‘noncoding’ (wrt. protein-alteration). ‘coding’ variants are here defined as those with an ‘exonic’ status, with the exception of synonymous variants |
Gene information
| Tag | Description |
|---|---|
ENTREZ_ID |
Entrez gene identifier |
APPRIS |
Principal isoform flags according to the APPRIS principal isoform database |
MANE_SELECT |
Indicating if the transcript is the MANE Select or MANE Plus
Clinical transcript for the gene (picked by VEP’s
--flag_pick_allele_gene option) |
UNIPROT_ID |
UniProt identifier |
UNIPROT_ACC |
UniProt accession(s) |
ENSEMBL_GENE_ID |
Ensembl gene identifier for VEP’s picked transcript (ENSGXXXXXXX) |
ENSEMBL_TRANSCRIPT_ID |
Ensembl transcript identifier for VEP’s picked transcript (ENSTXXXXXX) |
ENSEMBL_PROTEIN_ID |
Ensembl corresponding protein identifier for VEP’s picked transcript |
REFSEQ_MRNA |
Corresponding RefSeq transcript(s) identifier for VEP’s picked transcript (NM_XXXXX) |
TRANSCRIPT_MANE_SELECT |
MANE select transcript identifer: one high-quality representative transcript per protein-coding gene that is well-supported by experimental data and represents the biology of the gene |
TRANSCRIPT_MANE_PLUS_CLINICAL |
transcripts chosen to supplement MANE Select when needed for clinical variant reporting |
GENCODE_TAG |
tag for gencode transcript (basic etc) |
GENCODE_TRANSCRIPT_TYPE |
type of transcript (protein-coding etc.) |
CORUM_ID |
Associated protein complexes (identifiers) from CORUM |
TUMOR_SUPPRESSOR |
Indicates whether gene is predicted as a tumor suppressor gene, from Network of Cancer Genes (NCG) & the CancerMine text-mining resource |
TUMOR_SUPPRESSOR_EVIDENCE |
Underlying evidence for gene being a tumor suppressor. Format:
NCG:<TRUE|FALSE>&CancerMine:<LC|MC|HC>:num_citations
|
ONCOGENE |
Indicates whether gene is predicted as an oncogene, from Network of Cancer Genes (NCG) & the CancerMine text-mining resource |
ONCOGENE_EVIDENCE |
Underlying evidence for gene being an oncogene. Format:
NCG:<TRUE|FALSE>&CancerMine:<LC|MC|HC>:num_citations
|
INTOGEN_DRIVER |
Gene is predicted as a cancer driver in the IntoGen Cancer Drivers Database |
TCGA_DRIVER |
Gene is predicted as a cancer driver in the TCGA pan-cancer analysis of cancer driver genes and mutations |
PROB_EXAC_LOF_INTOLERANT |
dbNSFP_gene: the probability of being loss-of-function
intolerant (intolerant of both heterozygous and homozygous lof variants)
based on ExAC r0.3 data |
PROB_EXAC_LOF_INTOLERANT_HOM |
dbNSFP_gene: the probability of being intolerant of
homozygous, but not heterozygous lof variants based on ExAC r0.3
data |
PROB_EXAC_LOF_TOLERANT_NULL |
dbNSFP_gene: the probability of being tolerant of both
heterozygous and homozygous lof variants based on ExAC r0.3 data |
PROB_EXAC_NONTCGA_LOF_INTOLERANT |
dbNSFP_gene: the probability of being loss-of-function
intolerant (intolerant of both heterozygous and homozygous lof variants)
based on ExAC r0.3 nonTCGA subset |
PROB_EXAC_NONTCGA_LOF_INTOLERANT_HOM |
dbNSFP_gene: the probability of being intolerant of
homozygous, but not heterozygous lof variants based on ExAC r0.3 nonTCGA
subset |
PROB_EXAC_NONTCGA_LOF_TOLERANT_NULL |
dbNSFP_gene: the probability of being tolerant of both
heterozygous and homozygous lof variants based on ExAC r0.3 nonTCGA
subset |
PROB_GNOMAD_LOF_INTOLERANT |
dbNSFP_gene: the probability of being loss-of-function
intolerant (intolerant of both heterozygous and homozygous lof variants
based on gnomAD 2.1 data |
PROB_GNOMAD_LOF_INTOLERANT_HOM |
dbNSFP_gene: the probability of being intolerant of
homozygous, but not heterozygous lof variants based on gnomAD 2.1
data |
PROB_GNOMAD_LOF_TOLERANT_NULL |
dbNSFP_gene: the probability of being tolerant of both
heterozygous and homozygous lof variants based on gnomAD 2.1 data |
PROB_HAPLOINSUFFICIENCY |
dbNSFP_gene: Estimated probability of
haploinsufficiency of the gene (from http://dx.doi.org/10.1371/journal.pgen.1001154) |
ESSENTIAL_GENE_CRISPR |
dbNSFP_gene: Essential (E) or Non-essential
phenotype-changing (N) based on large scale CRISPR experiments. from http://dx.doi.org/10.1126/science.aac7041
|
ESSENTIAL_GENE_CRISPR2 |
dbNSFP_gene: Essential (E), context-Specific essential
(S), or Non-essential phenotype-changing (N) based on large scale CRISPR
experiments. from http://dx.doi.org/10.1016/j.cell.2015.11.015
|
Variant effect and protein-coding information
| Tag | Description |
|---|---|
MUTATION_HOTSPOT |
mutation hotspot codon in cancerhotspots.org. Format:
gene_symbol | codon | q-value
|
MUTATION_HOTSPOT_TRANSCRIPT |
hotspot-associated transcripts (Ensembl transcript ID) |
MUTATION_HOTSPOT_CANCERTYPE |
hotspot-associated cancer types (from cancerhotspots.org) |
UNIPROT_FEATURE |
Overlapping protein annotations from UniProt KB |
PFAM_DOMAIN |
Pfam domain identifier (from VEP) |
INTOGEN_DRIVER_MUT |
Indicates if existing variant is predicted as driver mutation from IntoGen Catalog of Driver Mutations |
PUTATIVE_DRIVER_MUTATION |
Variant is predicted as driver mutation in the TCGA pan-cancer analysis of cancer driver genes and mutations |
EFFECT_PREDICTIONS |
All predictions of effect of variant on protein function and
pre-mRNA splicing from database of
non-synonymous functional predictions - dbNSFP v4.2. Predicted
effects are provided by different sources/algorithms (separated by
&), T = Tolerated, N =
Neutral, D = Damaging: 1.SIFT, 2.MutationTaster (data release
Nov 2015), 3.MutationAssessor
(release 3), 4.FATHMM
(v2.3), 5.PROVEAN (v1.1
Jan 2015), 6.FATHMM_MKL,
7.PRIMATEAI,
8.DEOGEN2,
9.DBNSFP_CONSENSUS_RNN
(Ensembl/consensus prediction, based on deep learning), 10.SPLICE_SITE_EFFECT_ADA
(Ensembl/consensus prediction of splice-altering SNVs, based on adaptive
boosting), 11.SPLICE_SITE_EFFECT_RF
(Ensembl/consensus prediction of splice-altering SNVs, based on random
forest), 12.M-CAP, 13.MutPred, 14.GERP,
15.BayesDel, 16.LIST-S2, 17.ALoFT
|
DBNSFP_BAYESDEL_ADDAF |
predicted effect from BayesDel (dbNSFP) |
DBNSFP_LIST_S2 |
predicted effect from LIST-S2 (dbNSFP) |
DBNSFP_SIFT |
predicted effect from SIFT (dbNSFP) |
DBNSFP_PROVEAN |
predicted effect from PROVEAN (dbNSFP) |
DBNSFP_MUTATIONTASTER |
predicted effect from MUTATIONTASTER (dbNSFP) |
DBNSFP_MUTATIONASSESSOR |
predicted effect from MUTATIONASSESSOR (dbNSFP) |
DBNSFP_M_CAP |
predicted effect from M-CAP (dbNSFP) |
DBNSFP_ALOFTPRED |
predicted effect from ALoFT (dbNSFP) |
DBNSFP_MUTPRED |
score from MUTPRED (dbNSFP) |
DBNSFP_FATHMM |
predicted effect from FATHMM (dbNSFP) |
DBNSFP_PRIMATEAI |
predicted effect from PRIMATEAI (dbNSFP) |
DBNSFP_DEOGEN2 |
predicted effect from DEOGEN2 (dbNSFP) |
DBNSFP_GERP |
evolutionary constraint measure from GERP (dbNSFP) |
DBNSFP_FATHMM_MKL |
predicted effect from FATHMM-mkl (dbNSFP) |
DBNSFP_META_RNN |
predicted effect from ensemble prediction (deep learning - dbNSFP) |
DBNSFP_SPLICE_SITE_RF |
predicted effect of splice site disruption, using random forest (dbscSNV) |
DBNSFP_SPLICE_SITE_ADA |
predicted effect of splice site disruption, using boosting (dbscSNV) |
Variant frequencies/annotations in germline/somatic databases
| Tag | Description |
|---|---|
AFR_AF_GNOMAD |
African/American germline allele frequency (gnomAD release 2) |
AMR_AF_GNOMAD |
American germline allele frequency (gnomAD release 2) |
GLOBAL_AF_GNOMAD |
Adjusted global germline allele frequency (gnomAD release 2) |
SAS_AF_GNOMAD |
South Asian germline allele frequency (gnomAD release 2) |
EAS_AF_GNOMAD |
East Asian germline allele frequency (gnomAD release 2) |
FIN_AF_GNOMAD |
Finnish germline allele frequency (gnomAD release 2) |
NFE_AF_GNOMAD |
Non-Finnish European germline allele frequency (gnomAD release 2) |
OTH_AF_GNOMAD |
Other germline allele frequency (gnomAD release 2) |
ASJ_AF_GNOMAD |
Ashkenazi Jewish allele frequency (gnomAD release 2) |
AFR_AF_1KG |
1000G Project - phase 3 germline allele frequency for samples from AFR (African) |
AMR_AF_1KG |
1000G Project - phase 3 germline allele frequency for samples from AMR (Ad Mixed American) |
EAS_AF_1KG |
1000G Project - phase 3 germline allele frequency for samples from EAS (East Asian) |
EUR_AF_1KG |
1000G Project - phase 3 germline allele frequency for samples from EUR (European) |
SAS_AF_1KG |
1000G Project - phase 3 germline allele frequency for samples from SAS (South Asian) |
GLOBAL_AF_1KG |
1000G Project - phase 3 germline allele frequency for all 1000G project samples (global) |
DBSNPRSID |
dbSNP reference ID, as provided by VEP |
COSMIC_MUTATION_ID |
Mutation identifier in Catalog of somatic mutations in cancer database, as provided by VEP |
TCGA_PANCANCER_COUNT |
Raw variant count across all TCGA tumor types |
TCGA_FREQUENCY |
Frequency of variant across TCGA tumor types. Format:
tumortype| percent affected|affected cases|total cases
|
ICGC_PCAWG_OCCURRENCE |
Mutation occurrence in [ICGC |
ICGC_PCAWG_AFFECTED_DONORS |
Number of donors with the current mutation in [ICGC |
Clinical associations
| Tag | Description |
|---|---|
CLINVAR_MSID |
ClinVar Measure Set/Variant ID |
CLINVAR_ALLELE_ID |
ClinVar allele ID |
CLINVAR_PMID |
Associated Pubmed IDs for variant in ClinVar - germline state-of-origin |
CLINVAR_HGVSP |
Protein variant expression using HGVS nomenclature |
CLINVAR_PMID_SOMATIC |
Associated Pubmed IDs for variant in ClinVar - somatic state-of-origin |
CLINVAR_CLNSIG |
Clinical significance for variant in ClinVar - germline state-of-origin |
CLINVAR_CLNSIG_SOMATIC |
Clinical significance for variant in ClinVar - somatic state-of-origin |
CLINVAR_MEDGEN_CUI |
Associated MedGen concept identifiers (CUIs) - germline state-of-origin |
CLINVAR_MEDGEN_CUI_SOMATIC |
Associated MedGen concept identifiers (CUIs) - somatic state-of-origin |
CLINVAR_VARIANT_ORIGIN |
Origin of variant (somatic, germline, de novo etc.) for variant in ClinVar |
CLINVAR_REVIEW_STATUS_STARS |
Rating of the ClinVar variant (0-4 stars) with respect to level of review |
DOCM_PMID |
Associated Pubmed IDs for variant in Database of Curated Mutations |
OPENTARGETS_DISEASE_ASSOCS |
Associations between protein targets and disease based on multiple
lines of evidence (mutations, affected pathways, GWAS, literature etc).
Format: CUI:EFO_ID:IS_DIRECT:OVERALL_SCORE
|
OPENTARGETS_TRACTABILITY_COMPOUND |
Confidence for the existence of a modulator (small molecule) that interacts with the target to elicit a desired biological effect |
OPENTARGETS_TRACTABILITY_ANTIBODY |
Confidence for the existence of a modulator (antibody) that interacts with the target to elicit a desired biological effect |
Other
| Tag | Description |
|---|---|
CHEMBL_COMPOUND_ID |
antineoplastic drugs targeting the encoded protein (from Open Targets Platform, drugs are listed as ChEMBL compound identifiers) |
CIVIC_ID, CIVIC_ID_SEGMENT
|
Variant/segment (exon, codon) identifiers in the CIViC database |
CGI_ID, CGI_ID_SEGMENT
|
Variant/segment (exon, codon) identifier in the Cancer Genome Interpreter Cancer Biomarkers Database |
2. Tab-separated values (TSV)
We provide a tab-separated values file with most important annotations for SNVs/InDels. The file has the following naming convention:
<sample_id>.pcgr_acmg.<genome_assembly>.snvs_indels.tiers.tsv
The SNVs/InDels are organized into different tiers (as defined above for the HTML report)
The following variables are included in the tiered TSV file (VCF tags
issued by the user (--preserved_info_tags) will be appended
at the end):
| Variable | Description |
|---|---|
1. CHROM
|
Chromosome |
2. POS
|
Position (VCF-based) |
3. REF
|
Reference allele |
4. ALT
|
Alternate allele |
5. GENOMIC_CHANGE
|
Identifier for variant at the genome (VCF) level,
e.g. 1:g.152382569A>G. Format:
<chrom>:g.<position><ref_allele><alt_allele>
|
6. GENOME_VERSION
|
Assembly version, e.g. GRCh37 |
7. VCF_SAMPLE_ID
|
Sample identifier |
8. VARIANT_CLASS
|
Variant type, e.g. SNV/insertion/deletion |
9. SYMBOL
|
Gene symbol |
10. GENE_NAME
|
Gene description |
11. CCDS
|
CCDS identifier |
12. CANONICAL
|
indication of canonical transcript |
13. ENTREZ_ID
|
Entrez gene identifier |
14. UNIPROT_ID
|
UniProt protein identifier |
15. ENSEMBL_TRANSCRIPT_ID
|
Ensembl transcript identifier |
16. ENSEMBL_GENE_ID
|
Ensembl gene identifier |
17. REFSEQ_MRNA
|
RefSeq mRNA identifier |
18. REFSEQ_PEPTIDE
|
RefSeq peptide identifier |
19. TRANSCRIPT_MANE_SELECT
|
MANE select transcript identifier |
20. ONCOGENE
|
Gene is predicted/classified as an oncogene (CancerMine/NCG) |
21. ONCOGENE_EVIDENCE
|
Underlying evidence for oncogene prediction/classification |
22. TUMOR_SUPPRESSOR
|
Gene is predicted/classified as tumor suppressor (CancerMine/NCG) |
23. TUMOR_SUPPRESSOR_EVIDENCE
|
Underlying evidence for tumor suppressor prediction/classification |
24. CONSEQUENCE
|
Variant consequence (as defined above for VCF output: Consequence) |
25. PROTEIN_CHANGE
|
Protein change (HGVSp without reference accession) |
26. PROTEIN_DOMAIN
|
Protein domain description (Pfam) |
27. CODING_STATUS
|
Coding variant status wrt. protein alteration (coding
or noncoding) |
28. EXONIC_STATUS
|
Exonic variant status (exonic or
nonexonic) |
29. CDS_CHANGE
|
composite VEP-based variable for coding change, format:
Consequence:Feature:cDNA_position:EXON:HGVSp_short
|
30. HGVSp
|
|
31. HGVSc
|
|
32. REGULATORY_ANNOTATION
|
Regulatory annotations (promoter/enhancer/TF_binding site overlap etc.) from VEP (optional) |
33. EFFECT_PREDICTIONS
|
as defined above for VCF |
34. MUTATION_HOTSPOT
|
mutation hotspot codon in cancerhotspots.org. Format:
gene_symbol | codon | q-value
|
35. MUTATION_HOTSPOT_TRANSCRIPT
|
hotspot-associated transcripts (Ensembl transcript ID) |
36. MUTATION_HOTSPOT_CANCERTYPE
|
hotspot-associated cancer types (from cancerhotspots.org) |
37. PUTATIVE_DRIVER_MUTATION
|
Indicates if variant is predicted as driver mutation from TCGA’s PanCancer study of cancer driver mutation |
38. CHASMPLUS_DRIVER
|
Driver mutation predicted by CHASMplus algorithm |
39. CHASMPLUS_TTYPE
|
Tumor type for which mutation is predicted as driver by CHASMplus |
40. VEP_ALL_CSQ
|
all VEP transcript block consequences |
41. DBSNPRSID
|
dbSNP reference cluster ID |
42. COSMIC_MUTATION_ID
|
COSMIC mutation ID |
43. TCGA_PANCANCER_COUNT
|
Raw variant count across all TCGA tumor types |
44. TCGA_FREQUENCY
|
Frequency of variant across TCGA tumor types. Format:
tumortype | percent affected | affected cases | total cases
|
45. ICGC_PCAWG_OCCURRENCE
|
Mutation occurrence in ICGC-PCAWG by project:
project_code | affected_donors | tested_donors | frequency
|
46. CHEMBL_COMPOUND_ID
|
Compounds (as ChEMBL IDs) that are targeted towards the encoded protein (from Open Targets Platform) |
47. CHEMBL_COMPOUND_TERMS
|
Compounds (as drug names) that are targeted towards the encoded protein (from Open Targets Platform) |
48. SIMPLEREPEATS_HIT
|
Variant overlaps UCSC simpleRepeat sequence repeat track |
49. WINMASKER_HIT
|
Variant overlaps UCSC windowmaskerSdust sequence repeat track |
50. OPENTARGETS_RANK
|
OpenTargets association score (between 0 and 1) for gene (maximum across cancer phenotypes) |
51. CLINVAR
|
ClinVar association: variant origin and associated traits |
52. CLINVAR_CLNSIG
|
clinical significance of ClinVar variant |
53. GLOBAL_AF_GNOMAD
|
global germline allele frequency in gnomAD |
54. GLOBAL_AF_1KG
|
1000G Project - phase 3, germline allele frequency |
55. NCER_PERCENTILE
|
Genome-wide percentile score (10bp bins) from the non-coding Essential Regulation (ncER) algorithm |
56. CALL_CONFIDENCE
|
confidence indicator for somatic variant |
57. DP_TUMOR
|
sequencing depth at variant site (tumor sample) |
58. AF_TUMOR
|
allelic fraction of alternate allele (tumor sample) |
59. DP_CONTROL
|
sequencing depth at variant site (control sample) |
60. AF_CONTROL
|
allelic fraction of alternate allele (control sample) |
61. TIER
|
|
62. TIER_DESCRIPTION
|
3. Mutational signature contributions
We provide a tab-separated values file with information about mutational signatures detected in the tumor sample. The file has the following naming convention:
<sample_id>.pcgr_acmg.<genome_assembly>.mutational_signatures.tsv
The format of the TSV file is the following:
| Variable | Description |
|---|---|
1. signature_id
|
identifier for signature |
2. sample_id
|
sample identifier |
3. prop_signature
|
relative contribution of mutational signature |
4. group
|
keyword for signature aetiology |
5. all_reference_signatures
|
logical indicating if all reference signatures were used for reconstruction/inference |
6. tumor_type
|
tumor type (used for retrieval of reference signatures) |
7. reference_collection
|
collection used for reference signatures |
8. reference_signatures
|
signatures present in reference collection |
9. fitting_accuracy
|
accuracy of mutational signature fitting |
Copy number aberrations
1. Tab-separated values (TSV)
Copy number segments are intersected with the genomic coordinates of all transcripts from GENCODE’s basic gene annotation. In addition, PCGR attaches cancer-relevant annotations for the affected transcripts. The naming convention of the compressed TSV file is as follows:
-
<sample_id>.pcgr_acmg.<genome_assembly>.cna_segments.tsv.gz- NOTE: This file is organized according to the affected transcripts (i.e. one line/record per affected transcript).
The format of the compressed TSV file is the following:
| Variable | Description |
|---|---|
1. chrom
|
chromosome |
2. segment_start
|
start of copy number segment |
3. segment_end
|
end of copy number segment |
4. segment_id
|
segment identifier |
5. segment_length_Mb
|
length of segment in Mb |
6. event_type
|
focal or broad (covering more than 25% of chromosome arm) |
7. cytoband(s)
|
cytobands covered by segment |
8. LogR
|
Copy log-ratio |
9. sample_id
|
Sample identifier |
10. ensembl_gene_id
|
Ensembl gene identifier |
11. symbol
|
Gene symbol |
12. ensembl_transcript_id
|
Ensembl transcript identifier |
13. transcript_start
|
chromosomal position of transcript start |
14. transcript_end
|
chromosomal position of transcript end |
15. transcript_overlap_percent
|
percent of transcript length covered by CN segment |
16. name
|
gene name description |
17. biotype
|
type of gene |
18. tumor_suppressor
|
tumor suppressor gene status (CancerMine literature database/Network of Cancer Genes) |
19. oncogene
|
oncogene status (CancerMine literature database/Network of Cancer Genes) |
20. intogen_drivers
|
predicted driver gene status (IntoGen Cancer Drivers Database) |
21. chembl_compound_id
|
anti-cancer drugs that are targeted towards the encoded protein (from Open Targets Platform, drugs are listed as ChEMBL compound identifiers) |
22. gencode_tag
|
|
23. gencode_release
|