{"doi":"10.1186/s13073-021-00964-1","title":"Non-cancer-related pathogenic germline variants and expression consequences in ten-thousand cancer genomes","abstract":"<h4>Background</h4>DNA sequencing is increasingly incorporated into the routine care of cancer patients, many of whom also carry inherited, moderate/high-penetrance variants associated with other diseases. Yet, the prevalence and consequence of such variants remain unclear.<h4>Methods</h4>We analyzed the germline genomes of 10,389 adult cancer cases in the TCGA cohort, identifying pathogenic/likely pathogenic variants in autosomal-dominant genes, autosomal-recessive genes, and 59 medically actionable genes curated by the American College of Molecular Genetics (i.e., the ACMG 59 genes). We also analyzed variant- and gene-level expression consequences in carriers.<h4>Results</h4>The affected genes exhibited varying pan-ancestry and population-specific patterns, and overall, the European population showed the highest frequency of pathogenic/likely pathogenic variants. We further identified genes showing expression consequence supporting variant functionality, including altered gene expression, allelic specific expression, and mis-splicing determined by a massively parallel splicing assay.<h4>Conclusions</h4>Our results demonstrate that expression-altering variants are found in a substantial fraction of cases and illustrate the yield of genomic risk assessments for a wide range of diseases across diverse populations.","journal":"Genome Medicine","year":2021,"id":10209,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.2045,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-09-09","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":23572,"name":"Xiao Fan","orcid":"0000-0002-8526-6945","position":1,"is_corresponding":false},{"id":23573,"name":"Yufeng Shen","orcid":"0000-0002-1299-5979","position":2,"is_corresponding":false},{"id":23574,"name":"Meghana S. Pagadala","orcid":"0000-0002-7591-6035","position":3,"is_corresponding":false},{"id":23575,"name":"Rebecca Signer","orcid":"0000-0001-8564-4267","position":4,"is_corresponding":false},{"id":23576,"name":"Kamil J. Cygan","orcid":"0000-0003-2088-474X","position":5,"is_corresponding":false},{"id":23577,"name":"William G. Fairbrother","orcid":"0000-0002-6312-5615","position":6,"is_corresponding":false},{"id":2188,"name":"Hannah Carter","orcid":"0000-0002-1729-2463","position":7,"is_corresponding":false},{"id":23578,"name":"Wendy K. Chung","orcid":"0000-0003-3438-5685","position":8,"is_corresponding":false},{"id":1998,"name":"Kuan-lin Huang","orcid":"0000-0002-3237-4248","position":9,"is_corresponding":false},{"id":23571,"name":"Zishan Wang","orcid":"0000-0002-5980-4711","position":0,"is_corresponding":true}],"reference_count":44,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-03-01T18:20:47.508186Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}