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Specifications of the ACMG/AMP variant interpretation guidelines for germline TP53 variants
- Source :
- Human mutation, vol 42, iss 3
- Publication Year :
- 2021
- Publisher :
- eScholarship, University of California, 2021.
-
Abstract
- Germline pathogenic variants in TP53 are associated with Li-Fraumeni syndrome, a cancer predisposition disorder inherited in an autosomal dominant pattern associated with a high risk of malignancy, including early-onset breast cancers, sarcomas, adrenocortical carcinomas, and brain tumors. Intense cancer surveillance for individuals with TP53 germline pathogenic variants is associated with reduced cancer-related mortality. Accurate and consistent classification of germline variants across clinical and research laboratories is important to ensure appropriate cancer surveillance recommendations. Here, we describe the work performed by the Clinical Genome Resource TP53 Variant Curation Expert Panel (ClinGen TP53 VCEP) focused on specifying the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines for germline variant classification to the TP53 gene. Specifications were developed for 20 ACMG/AMP criteria, while nine were deemed not applicable. The original strength level for the 10 criteria was also adjusted due to current evidence. Use of TP53-specific guidelines and sharing of clinical data amongexperts and clinical laboratories led to a decrease in variants of uncertain significance from 28% to 12% compared with the original guidelines. The ClinGen TP53 VCEP recommends the use of these TP53-specific ACMG/AMP guidelines as the standard strategy for TP53 germline variant classification.
- Subjects :
- Genetics & Heredity
Prevention
Human Genome
Clinical Sciences
Genetic Variation
United States
Li-Fraumeni Syndrome
ClinGen TP53 Variant Curation Expert Panel
Germ Cells
pathogenic variant
Good Health and Well Being
Genetics
Humans
cancer
2.1 Biological and endogenous factors
Genetic Testing
TP53
variant curation
Tumor Suppressor Protein p53
Aetiology
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Human mutation, vol 42, iss 3
- Accession number :
- edsair.od.......325..d4ccaad6db38dc4b55c80caff6e12904