ArticleAmerican journal of human genetics2012
Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes.
Article in American journal of human genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07652580 (Toxin Exposure and Immune Dysregulation in Non-Hodgkin Lymphoma Across the Military Healthcare System), which is not on this map. Cited by 134 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Toxin Exposure and Immune Dysregulation in Non-Hodgkin Lymphoma Across the Military Healthcare System
Who cites it
134 citing papers in PubMed, 3 syntheses or guidelines pooled it, 207 citations in OpenAlex.
- Secondary findings in hereditary cancer genes after germline genetic testing - systematic review of literature.Human genetics · 2025Pooled it
- A systematic literature review of disclosure practices and reported outcomes for medically actionable genomic secondary findings.Genetics in medicine : official journal of the American College of Medical Genetics · 2021Pooled it
- ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.Genetics in medicine : official journal of the American College of Medical Genetics · 2013Guideline
- Alterations in DNA Damage Response and Repair Genes as Potential Marker of Clinical Benefit From PD-1/PD-L1 Blockade in Advanced Urothelial Cancers.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2018Trial
- Design of a randomized controlled trial for genomic carrier screening in healthy patients seeking preconception genetic testing.Contemporary clinical trials · 2017Trial
- Mutational spectrum of BRCA genes in Egyptian patients with breast cancer.Scientific reports · 2025Article
- Incidental findings related to genes associated to HAE-nC1INH: how to proceed?Frontiers in immunology · 2025Review
- Prevalence of BRCA1, BRCA2, and PALB2 genomic alterations among 924 Taiwanese breast cancer assays with tumor-only targeted sequencing: extended data analysis from the VGH-TAYLOR study.Breast cancer research : BCR · 2023Article
- A Case Study on PPM1D and 9 Other Shared Germline Alterations in a Family.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- Genotype first: Clinical genomics research through a reverse phenotyping approach.American journal of human genetics · 2023Review
- Case report: A safeguard in the sea of variants of uncertain significance: a case study on child with high risk neuroblastoma and acute myeloid leukemia.Frontiers in oncology · 2023Article
- Delivering precision oncology to patients with cancer.Nature medicine · 2022Review
- Article
- Classification of the canonical splice alterationCold Spring Harbor molecular case studies · 2022Article
- Incomplete Penetrance and Variable Expressivity: From Clinical Studies to Population Cohorts.Frontiers in genetics · 2022Review
- To disclose, or not to disclose? Perspectives of clinical genomics professionals toward returning incidental findings from genomic research.BMC medical ethics · 2021Article
- Article
- Implications of the germline variants of DNA damage response genes detected by cancer precision medicine for radiological risk communication and cancer therapy decisions.Journal of radiation research · 2021Review
- Disclosure of secondary findings in exome sequencing of 2480 Japanese cancer patients.Human genetics · 2021Article
- GermlineFrontiers in endocrinology · 2021Article
74 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Genome- and exome-sequencing costs are continuing to fall, and many individuals are undergoing these assessments as research participants and patients. The issue of secondary (so-called incidental) findings in exome analysis is controversial, and data are needed on methods of detection and their frequency. We piloted secondary variant detection by analyzing exomes for mutations in cancer-susceptibility syndromes in subjects ascertained for atherosclerosis phenotypes. We performed exome sequencing on 572 ClinSeq participants, and in 37 genes, we interpreted variants that cause high-penetrance cancer syndromes by using an algorithm that filtered results on the basis of mutation type, quality, and frequency and that filtered mutation-database entries on the basis of defined categories of causation. We identified 454 sequence variants that differed from the human reference. Exclusions were made on the basis of sequence quality (26 variants) and high frequency in the cohort (77 variants) or dbSNP (17 variants), leaving 334 variants of potential clinical importance. These were further filtered on the basis of curation of literature reports. Seven participants, four of whom were of Ashkenazi Jewish descent and three of whom did not meet family-history-based referral criteria, had deleterious BRCA1 or BRCA2 mutations. One participant had a deleterious SDHC mutation, which causes paragangliomas. Exome sequencing, coupled with multidisciplinary interpretation, detected clinically important mutations in cancer-susceptibility genes; four of such mutations were in individuals without a significant family history of disease. We conclude that secondary variants of high clinical importance will be detected at an appreciable frequency in exomes, and we suggest that priority be given to the development of more efficient modes of interpretation with trials in larger patient groups.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.