肿瘤基因检测的解读流程

/1FASTQBWAGRCh37/38NCBIhg19/hg38UCSCPicardGATKSNVIndelANNOVAR.vcf11vcfvcfChrStartEndRefAltFunc.refGeneexonicintronicUTR3UTR5splicingupstreamdownstreamintergenicexonicUTRGene.refGeneGeneDetail.refGeneExonicFunc.refGeneframeshiftinsertionframeshiftdeletionstopgainstoplossnonframeshiftinsertionnonframeshiftdeletionsynonymousSNVnonsynonymousSNV.AAChange.refGenevcfCLINSIGClinVarBenignLikelybenignUncertainsignificanceLikelypathogenicPathogenicDrug-responseCLINDBNCLINACCVariantAccessionandVersionsCLINSDBCLINSDBIDPopFreqMax1000_All1000_AFR1000_AMR1000_EAS1000_EUR1000_SASSnp138dbSNPIDCosmic70COSMICIDESP6500siv2_ALLESP6500ESP6500siv2_AAESP6500ESP6500siv2_EAESP6500ExAC_AllExACExAC_AFRExACExAC_AMRExACExAC_EASExACExAC_FINExACExAC_NFEExACExAC_OTHExACExAC_SASExACCG46CG46CG46CompleteGenomicsBGI46201720000ICGC_IdIDICGC_OccurrenceICGCCOCA-CN|1|187|0.00535://:28132688Omim_phenotypeOMIMQUALQ=-10log10(e)FILTERFILTERFILTERPASSFILTERPASSotherFILTERflag.INFO&FORMATGT:AD:AF:ALT_F1R2:ALT_F2R1:FOXOG:QSS:REF_F1R2:REF_F2R1GT0REF1Alt2AltADREFAltreadsREFAltAFAltNORMALTUMORSIFTprediction(T:tolerated;D:deleterious)PolyPhenHumanDivprediction(D:Probablydamaging,P:possiblydamaging;B:benign)LTRMutTasterMutationAssessorFATHMMCADDGERP++2pannelTumormutationburdenPD1/PD-L1(ORR)(PFS)(DCB)5%1%ExonicFunc.refGene.synonymousSNVunknownPopFreqMax0.1%.EGFRJAKB2MDNA0-8BRAFKRASAPCCTNNB1PIK3CAKRASKRASPIK3CARB1VHLresponsiveresistantdriverpassenger2017AssociationforMolecularPathology,AMPAmericanSocietyofClinicalOncologyCollegeofAmericanPathologistsHGVSPMID:27993330NCBI1000GExACCOSMICICGCHGMDClinVarPolyPhen2HumanSplicingFindervariantswithstrongclinicalsignificanceLevelALevelBvariantswithpotentialclinicalsignificanceLevelCLevelDvariantsofunknownclinicalsignificancevariantsdeemedbenignorlikelybenign/LevelAFDANCCNLevelBLevelCFDALevelD2recurrentmutationEGFRTK18~21TK3019delE746-A75021L858R2020T790ML858QD761YT854AHER22030%HER22-4%p.S310,p.L755p.G776L,p.V777Lp.S855Ip.N857SBRAFV600EPubmedBRAF1%3%V600EBRAFG466VG469AD594GvemurafenibBRAFV600EBRAFV600E2PMID:24479672CivicOncoKBPersonalizedcancertherapyClinicalKnowledgebaseSIFTPolyPhen2MutationAssessorTP53DNAvcfSIFT0.05PolyPhen20.3MutationAssessor8PMID:2381952118,000PMID:23334667173SMOHedgehog5AKT1PI3K-AKT-mTOR6mTOR15%12(CHPO)34562013ACGM/BRCA1BRCA2TP53STK11MLH1MSH2MSH6PMS2APCMUTYHVHLMEN1RETPTENRB1SDHCSDHDTSC1TSC2WT1NF2PMID23788249N_Freq40%+c.__+p.__googleNCBIHGMDOMIMACMGInterVarexonAmericanCollegeofMedicalGeneticsandGenomics,ACMGAssociationforMolecularPathology,AMP2015PMID:25741868HumanGenomeVariationSociety,HGVSpopulationdatacomputationaldatafunctionaldatapathogeniclikelypathogenicuncertainsignificancelikelybenignbenign/PVS1PS1-4PM1-6PP1-5/BA1BS1-4BP1-6causativeactionableIncidentalFindings3FDANCCNFDANCCNFDA/NCCNAMP//