InSiGHT-ClinGen Polyposis/Colon Cancer Variant Curation Expert Panel

InSiGHT-ClinGen 息肉病/结肠癌变异治疗专家组

• 批准号: 10426086
• 负责人: MARC S GREENBLATT
• 金额: $ 26.82万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-10 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10426086
• 关键词: APC gene; Accounting; Address; Age of Onset; American; Area; BMPR1A gene; Benign; Bioinformatics; Biological Assay; Classification; ClinVar; Clinical; Clinical Pathology; Colon; Colon Carcinoma; Colorectal Cancer; Communities; Custom; DNA; DNA Databases; Databases; Development; Diagnosis; Discipline; Disease; Familial colorectal cancer; Family; Funding; Future; Genes; Genetic; Genetic Diseases; Genetic testing for cancer risk; Genome; Genomics; Germ Lines; Goals; Hereditary Malignant Neoplasm; Hereditary Nonpolyposis Colorectal Neoplasms; Human Resources; Individual; Inherited; International; Link; MADH4 gene; Malignant neoplasm of gastrointestinal tract; Medical Genetics; Mismatch Repair; Oncogenes; Participant; Pathogenicity; Patients; Phenotype; Precancerous Polyp; Procedures; Recording of previous events; Reporting; Research; Research Personnel; Resources; Risk Assessment; STK11 gene; Scientist; Societies; Structure; Susceptibility Gene; Syndrome; System; Testing; Time; Training; United States National Institutes of Health; Variant; clinical infrastructure; clinically relevant; clinically significant; colorectal cancer risk; gastrointestinal; gene panel; gene repair; genetic counselor; genetic panel test; genetic testing; genetic variant; in silico; informatics infrastructure; insight; international scientific organization; medical schools; member; molecular diagnostics; molecular pathology; multidisciplinary; polyposis; precision medicine; premalignant; risk variant; tool; tumor; variant of unknown significance; working group

ABSTRACT: InSiGHT-ClinGen Polyposis /Colon Cancer (ICPC) Variant Curation Expert Panel (VCEP) The goal of the InSiGHT-ClinGen Polyposis /Colon Cancer (ICPC) Variant Curation Expert Panel (VCEP) is to create and maintain a multidisciplinary panel of Biocurators and Experts to curate the pathogenicity of genetic variants for genes associated with Colon Polyposis and Hereditary Colorectal Cancer (CRC). The NIH has prioritized identifying genomic variants associated with diseases of high priority and systematically determining their clinical significance for diagnosis and treatment. The Clinical Genome (ClinGen) project, NIH-funded since 2013, is dedicated to defining the clinical relevance of genes and variants for use in precision medicine and research. Our ICPC VCEP addresses a major clinical need, that of curating multiple genes that predispose to polyposis and hereditary CRC, which are common indications for genetic testing for cancer risk assessment. The VCEP represents a merger of two major efforts: 1) Classification of genetic variants by the International Society for Gastrointestinal Hereditary Tumors (InSIGHT), which has been ongoing by the InSIGHT Variant Interpretation Committee (VIC) since 2011, but has been limited to variants in the Mismatch Repair (MMR) genes that cause Lynch syndrome. 2) The ClinGen Colon Cancer Gene Curation Expert Panel (CRC GCEP), an unfunded working group (WG). The CRC GCEP, Co-chaired by the Co-PIs of this proposal, has evaluated gene-phenotype associations (Seifert 2019) but has not curated individual variants. Also, the ClinGen Sequence Variant Interpretation (SVI) working group has been refining variant curation rules established by the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology. Members of these teams (InSiGHT VIC and ClinGen CRC GCEP, with input from the ClinGen SVI) are primed to expand variant curation efforts to new colon cancer and polyposis risk genes. Our ICPC VCEP plan provides the necessary administrative structure for sustainable ongoing curation activities for multiple genes. Specific Aims are: 1) Create and maintain a VCEP of Biocurators, Coordinator, and Experts to curate the pathogenicity of genetic variants for genes associated with Colon Polyposis and Hereditary CRC; 2) Analyze and classify variants from: APC, MUTYH, STK11, SMAD4, BMPR1A, POLE, & POLD1 genes; 3) Perform gene-phenotype curation on genes with some reported evidence of association with polyposis or colorectal cancer, but not yet found to be Definitive or Strong, to guide future VCEP efforts. We will utilize the procedures, interfaces, tools and informatics infrastructure from ClinGen and the NCBI ClinVar database. Collectively, the VCEPs PIs and Co-Is have the scientific, clinical, and administrative expertise to advance variant curation efforts for a common, important pre-cancerous clinical condition, hereditary polyposis and CRC.

摘要：Insight-Clingen息肉病 /结肠癌（ICPC）变体策展专家小组（VCEP） 洞察息肉病 /结肠癌（ICPC）变体专家小组（VCEP）的目标是 创建和维护一个生物效力和专家的多学科小组，以策划遗传的致病性 与结肠息肉病和遗传结直肠癌（CRC）相关的基因变体。 NIH有 优先确定与高优先级和系统确定疾病相关的疾病相关的基因组变异 它们在诊断和治疗方面的临床意义。 NIH资助的临床基因组（Clingen）项目 自2013年以来，致力于定义基因和变体用于精密医学的临床相关性 和研究。我们的ICPC VCEP满足了主要的临床需求，即策划多种基因的临床需求 息肉病和遗传性CRC，这是癌症风险评估的基因检测的常见迹象。 VCEP代表了两项重大努力的合并：1）国际遗传变异的分类 胃肠道遗传肿瘤学会（Insight），这是由洞察变体进行的 自2011年以来的解释委员会（VIC），但仅限于不匹配维修（MMR）的变体 引起林奇综合征的基因。 2）克林根结肠癌基因策展专家小组（CRC GCEP）， 一个无资金的工作组（WG）。由本提案的共同主持的CRC GCEP评估了 基因 - 表型关联（Seifert 2019），但尚未策划个体变体。另外，金属 序列变体解释（SVI）工作组一直在完善由该规则建立的变体策划规则 美国医学遗传学学院（ACMG）和分子病理协会。 这些团队的成员（Insight VIC和Clingen CRC GCEP，Clingen SVI的输入） 为了扩大新结肠癌和多杂种风险基因的变异策划工作。我们的ICPC VCEP计划提供 多个基因可持续持续策划活动的必要行政结构。具体的 目的是：1）创建和维护生物效果，协调员和专家的VCEP，以策划致病性 与结肠多杂种和遗传性CRC相关的基因的遗传变异； 2）分析和分类 从：APC，MUTYH，STK11，SMAD4，BMPR1A，POL和POLD1基因的变体； 3）执行基因表型 策划与一些报道的基因相关的息肉病或大肠癌相关的证据，但尚未 被发现是确定的或强大的，以指导未来的VCEP努力。我们将利用过程，接口，工具 以及Clingen和NCBI Clinvar数据库的信息基础架构。总体而言，vceps pis和 共同具有科学，临床和行政专业知识，可以推进变体的策划工作 常见的，重要的癌前临床状况，遗传性息肉病和CRC。