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Although multiple guidelines exist, they do not provide a comprehensive, flexible approach covering all available evidence lines. Individual UK laboratories use local standards based on different publications, but a unified national framework is lacking. UK SVIG-UK (formed in 2018) reviewed existing systems and built a standardized UK-wide framework for solid and haematological cancers, updated through community engagement and ratified by UK ACGS.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/association-for-clinical-genomic-science-acgs-guidelines-for-the-classification-of-oncogenicity-of-somatic-variants-in-cancer-recommendations-by-the-uk-somatic-variant-interpretation-group-svig-uk/356518/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/association-for-clinical-genomic-science-acgs-guidelines-for-the-classification-of-oncogenicity-of-somatic-variants-in-cancer-recommendations-by-the-uk-somatic-variant-interpretation-group-svig-uk/356518.png","ImageObject",300,407,{"name":92,"@type":93},"Rhys","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-03","2026-09-23",true,{"@type":102,"interactionType":103,"userInteractionCount":29},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is a standardized approach needed for somatic variant interpretation in cancer genomics?","Question",{"text":112,"@type":113},"Comprehensive genomic testing requires interpreting somatic variants beyond known driver hotspots. Current guidelines lack a comprehensive, flexible evidence framework, and UK laboratories use differing local standards, creating a need for national standardization.","Answer",{"name":115,"@type":110,"acceptedAnswer":116},"What is SVIG-UK and how was its framework developed?",{"text":117,"@type":113},"SVIG-UK was formed in September 2018 by key stakeholders across the UK cancer genomics diagnostic community. It reviewed existing classification systems, identified differences in evidence use, then developed a single standardized UK-wide approach for both solid and haematological cancers.",{"name":119,"@type":110,"acceptedAnswer":120},"How does the SVIG-UK framework support clinical use of somatic variant assessments?",{"text":121,"@type":113},"The recommendations provide a standardized, comprehensive, and flexible method to classify the oncogenicity of somatic variants in cancer genes. The document also describes a two-step process: biological classification of oncogenic potential followed by an actionability assessment of clinical significance within a specific tumour context.","https://schema.org",{"og:url":83,"og:type":124,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":126,"canonical":83},"index,follow",{"doc_id":128,"site_id":62},356518,1791173773,{"code":4,"msg":5,"data":131},{"doc_id":128,"user_id":132,"nickname":92,"user_avatar":133,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":29,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":52,"language":139,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":67,"update_tm":143,"read_time":144},687207024643,"https://ap-avatar.wpscdn.com/davatar_3d24733baf745e90a7e4bdd5f77d97b2","Cancer genetics  \nOriginal research  \nAssociation for Clinical Genomic Science (ACGS) guidelines for the classification of oncogenicity of somatic variants in cancer: recommendations by the UK somatic variant interpretation group (SVIG-UK)  \nGeorge J Burghel  , 1,2 Joanne Mason,3 Kevin Baker,4 Kate Moloney,4  \nClaire Holt McKeeve, 5 Ashley Cartwright,6 Ana M Brás-Goldberg,3 Debbie Travis,6 Siân Lewis,7 Jennifer A Fairley,8 Jonathan Williams,9 Kirsty Russell, 10  \nSuzanne MacMahon, 11 Christopher Wragg 12  \n► Additional supplemental material is published online only. To view, please visit the journal online ([https://doi.org/](https://doi.org/)[ ](https://doi.org/)[10.1136/jmg-2025-111046](10.1136/jmg-2025-111046)) .  \nFor numbered affiliations see end of article.  \nCorrespondence to  \nDr George J Burghel;  \n[George.Burghel@mft.nhs.uk](George.Burghel@mft.nhs.uk)  \nGJB, JM, KB, KM and CW contributed equally.  \nReceived 7 July 2025 Accepted 29 October 2025  \n© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.  \nTo cite: Burghel GJ, Mason J, Baker K, et al. J Med Genet Epub ahead of print: [please include Day Month Year] . doi:10 . 1136/jmg-2025- 111046  \nABSTRACT  \nComprehensive genomic testing in routine cancer care pathways has created the need to interpret the consequences of somatic (acquired) genomic variants beyond the currently well-characterised driver variants in cancer gene hotspots. While several guidelines have been published to determine the oncogenicity of somatic cancer gene variants, they lack a comprehensive and flexible approach that encompasses all available lines of evidence. Individual UK laboratories have developed local approaches to standardise somatic variant interpretation, often based on different sets of published guidelines, but a comprehensive national standardised framework is lacking. The absence of standardisation in approaches to somatic variant interpretation highlightsa significant gap in the field of genomic medicine within the UK healthcare system. Key stakeholders from across the UK cancer genomics diagnostic community formed the UK Somatic Variant Interpretation Group (SVIG-UK) in September 2018 to develop a consensus approach for interpretation of somatic variants identified through genomic testing in patients with solid tumours and haematological malignancies. SVIG-UK scientists conducted a review of existing somatic variant interpretation classification systems and although they mostly agreed on evidence sources for variant interpretation, differences were identified in how the evidence should be used, weighted and combined. The SVIG-UK team subsequently developed a single, standardised UK-wide approach to somatic variant interpretation which encompassed both solid tumour and haematological cancer genomic testing. This framework was shared with stakeholders across the UK alongside variants for preliminary testing. Outcomes were then reviewed and following engagement sessions across the community, the variant interpretation recommendations were updated and ratified by the UK Association of Clinical Genomics Sciences. We present herein the SVIG-UK framework and recommendations, which provide a standardised, comprehensive and flexible approach for classifying the oncogenicity of somatic variants in cancer genes.  \nINTRODUCTION  \nThe complex process of oncogenesis is the result of sequential accumulation of ‘“driver’ genomic alterations within tumour cells. The accepted definition  \nWHAT IS ALREADY KNOWN ON THIS TOPIC  \n\n| ⇒ Variant interpretation is key in cancer genomics at both the inherited and somatic level. Germline variant interpretation in cancer and rare disease is well embedded in clinical practice guided by multiple sets of recommendations. Somatic cancer variant interpretation lags behind and is less well embedded in clinical practice. Very few guidelines are available with less flexib","cbCaipeErKUX419K","https://ap.wps.com/l/cbCaipeErKUX419K","pdf",997623,"English","# Abstract\n# Introduction\n# What is already known on this topic\n# What this study adds\n# How this study might affect research, practice or policy","[{\"question\":\"Why is a standardized approach needed for somatic variant interpretation in cancer genomics?\",\"answer\":\"Comprehensive genomic testing requires interpreting somatic variants beyond known driver hotspots. Current guidelines lack a comprehensive, flexible evidence framework, and UK laboratories use differing local standards, creating a need for national standardization.\"},{\"question\":\"What is SVIG-UK and how was its framework developed?\",\"answer\":\"SVIG-UK was formed in September 2018 by key stakeholders across the UK cancer genomics diagnostic community. It reviewed existing classification systems, identified differences in evidence use, then developed a single standardized UK-wide approach for both solid and haematological cancers.\"},{\"question\":\"How does the SVIG-UK framework support clinical use of somatic variant assessments?\",\"answer\":\"The recommendations provide a standardized, comprehensive, and flexible method to classify the oncogenicity of somatic variants in cancer genes. The document also describes a two-step process: biological classification of oncogenic potential followed by an actionability assessment of clinical significance within a specific tumour context.\"}]","Association for Clinical Genomic Science (ACGS) guidelines for the classification of oncogenicity of somatic variants in cancer - recommendations by the UK somatic variant interpretation group (SVIG-UK) | PDF",1790125772,25]