ArticleGenetics in medicine : official journal of the American College of Medical Genetics2017
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 425 papers.
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425 citing papers in PubMed.
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- Variants in human CD48 lead to impaired T cell immunity and increased inflammation.The Journal of clinical investigation · 2026Article
- Using patient-reported outcomes from the PROCLAIM trial to assess the impact of universal germline genetic testing for prostate cancer patients.Prostate cancer and prostatic diseases · 2026Article
- Expanding the Mutational Spectrum ofGenes · 2026Article
- Integrated Germline and Somatic Molecular Profiling to Detect Cancer Predisposition Has a High Clinical Impact in Poor-Prognosis Pediatric Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Co-occurring rare germline DNA repair gene variants in BRCA1/BRCA2 implicated hereditary breast cancer families.NPJ breast cancer · 2026Article
- LAMA2 Triple Variant in a Mexican Child with Congenital Muscular Dystrophy.Annals of Indian Academy of Neurology · 2026Article
- Ten tips for ordering, interpreting, and communicating genetic test results in nephrology.Clinical kidney journal · 2026Review
- Analytic Choices Shape Genomic Risk Estimates from Electronic Health Records: Coronary Heart Disease in eMERGE IV.medRxiv : the preprint server for health sciences · 2026Article
365 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Erratum issued
Authors and funding
12 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PurposeThe 2015 American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines were a major step toward establishing a common framework for variant classification. In practice, however, several aspects of the guidelines lack specificity, are subject to varied interpretations, or fail to capture relevant aspects of clinical molecular genetics. A simple implementation of the guidelines in their current form is insufficient for consistent and comprehensive variant classification.MethodsWe undertook an iterative process of refining the ACMG-AMP guidelines. We used the guidelines to classify more than 40,000 clinically observed variants, assessed the outcome, and refined the classification criteria to capture exceptions and edge cases. During this process, the criteria evolved through eight major and minor revisions.ResultsOur implementation: (i) separated ambiguous ACMG-AMP criteria into a set of discrete but related rules with refined weights; (ii) grouped certain criteria to protect against the overcounting of conceptually related evidence; and (iii) replaced the "clinical criteria" style of the guidelines with additive, semiquantitative criteria.ConclusionSherloc builds on the strong framework of 33 rules established by the ACMG-AMP guidelines and introduces 108 detailed refinements, which support a more consistent and transparent approach to variant classification.
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