Reporting genomic secondary findings: ACMG members weigh in

Scheuner, Maren T.; Peredo, Jane; Benkendorf, Judith; Bowdish, Bruce; Feldman, Gerald L.; Fleisher, Lloyd N.; Mulvihill, John J.; Watson, Michael S.; Herman, Gail E.; Evans, James P.

doi:10.1038/gim.2014.165

Cited by 53 publications

(41 citation statements)

References 17 publications

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“…Informed consent is necessary, and reporting of secondary findings should be optional. " 4 The ACMG Board of Directors created the ACMG Secondary Findings Maintenance Working Group (SFWG) in 2014 to define and implement a process for updating the SF list. In March 2015, the process for nominating revisions to the list was announced to the ACMG community.…”

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confidence: 99%

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics

Kalia

Adelman

Bale³

et al. 2017

Genetics in Medicine

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mentioning

confidence: 99%

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics

Kalia

Adelman

Bale³

et al. 2017

Genetics in Medicine

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1,377

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“…Therefore, to harmonize the current evidence available for each gene we have applied general concepts of tumour predisposition genes 49 and the 'review status' established by ClinVar, the public archive of reports of the relationships among human variations and phenotypes curated by the National Center for Biotechnology Information (NCBI). ClinVar uses a five-level rank of evidence to establish variant pathogenicity that was suggested by the American College of Medical Genetics and Genomics 50,51 (TABLE 2). In this Consensus Statement, we adopted a modified version of ClinVar's 'gold star' scale to create three PPGLs panel types based on the current evidence of involvement of these genes in PPGLs susceptibility at the germ line (the basic premise for hereditary PPGLs screening) and somatic level.…”

Section: Box 1 | Features Unique To Ppglsmentioning

confidence: 99%

Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas

et al. 2016

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Phaeochromocytomas and paragangliomas (PPGLs) are neural-crest-derived tumours of the sympathetic or parasympathetic nervous system that are often inherited and are genetically heterogeneous. Genetic testing is recommended for patients with these tumours and for family members of patients with hereditary forms of PPGLs. Due to the large number of susceptibility genes implicated in the diagnosis of inherited PPGLs, next-generation sequencing (NGS) technology is ideally suited for carrying out genetic screening of these individuals. This Consensus Statement, formulated by a study group comprised of experts in the field, proposes specific recommendations for the use of diagnostic NGS in hereditary PPGLs. In brief, the study group recommends target gene panels for screening of germ line DNA, technical adaptations to address different modes of disease transmission, orthogonal validation of NGS findings, standardized classification of variant pathogenicity and uniform reporting of the findings. The use of supplementary assays, to aid in the interpretation of the results, and sequencing of tumour DNA, for identification of somatic mutations, is encouraged. In addition, the study group launches an initiative to develop a gene-centric curated database of PPGL variants, with annual re-evaluation of variants of unknown significance by an expert group for purposes of reclassification and clinical guidance.

Funding Agencies|Cancer Prevention and Research Institute of Texas (CPRIT) [RP101202, RP57154]; Department of Defense [CDMRP W81XWH-12-1-0508]; Voelcker Fund; National Institutes of Health (NIH)s National Center for Research Resources; National Center for Advancing Translational Sciences [8UL1TR000149]; INSERM; French National Cancer Institute (INCA); Direction Generale de lOffre de Soins (DGOS); INCA [INCA-DGOS_8663]; European Union [633983]; Brazilian National Council for Scientific and Technological Development (CNPq); Cancer Research for PErsonalized Medicine (CARPEM); ERC Advanced Researcher Award

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“…In early 2014, they emailed a survey link to the membership, with the results published in November. The survey found high agreement (80.7% combining “agree” and “strongly agree”) that patients “should be able to opt out of laboratory analysis of the 56 genes on the ACMG list.” 16 There was less agreement that patients “should be able to decide which genes will be analyzed for pathogenic variants among the 56 genes on the ACMG list” (46.2% combining “agree” and strongly agree”), though only 34.8% rejected this idea (combining “disagree” and “strongly disagree”). 17 There was no consensus on how to manage secondary or incidental findings in children.…”

Section: Acmg 2014mentioning

confidence: 99%

The Continuing Evolution of Ethical Standards for Genomic Sequencing in Clinical Care: Restoring Patient Choice

Wolf¹

2017

J. Law. Med. Ethics

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Developing ethical standards for clinical use of large-scale genome and exome sequencing has proven challenging, in part due to the inevitability of incidental or secondary findings. Policy of the American College of Medical Genetics and Genomics (ACMG) has evolved but remains problematic. In 2013, ACMG issued policy recommending mandatory analysis of 56 extra genes whenever sequencing was ordered for any indication, in order to ascertain positive findings in pathogenic and actionable genes. Widespread objection yielded a 2014 amendment allowing patients to opt-out from analysis of the extra genes. In 2015, ACMG published the amended policy, providing that patients could opt out of the full set of extra genes, but not a subset. In 2016, ACMG enlarged the set and indicated planned expansion of the roster of extra genes to include pharmacogenetic findings. ACMG policy does not protect the respect for patient choice that prevails in other domains of clinical medicine, where informed consent allows patients to opt in to desired testing. By creating an expanding domain of genomic testing that will be routinely conducted unless patients reject the entire set of extra tests, ACMG creates an exceptional domain clinical practice that is not supported by ethics or science.

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Reporting genomic secondary findings: ACMG members weigh in

Cited by 53 publications

References 17 publications

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics

Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics

Consensus Statement on next-generation-sequencing-based diagnostic testing of hereditary phaeochromocytomas and paragangliomas

The Continuing Evolution of Ethical Standards for Genomic Sequencing in Clinical Care: Restoring Patient Choice

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