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Title: A Collaborative Effort to Define Classification Criteria for ATM Variants in Hereditary Cancer Patients
Author: Feliubadaló i Elorza, Maria Lídia
Moles Fernández, Alejandro
Santamariña-Pena, Marta
Sánchez, Alysson T.
López Novo, Anael
Porras, Luz Marina
Blanco, Ana
Capellá, G. (Gabriel)
Hoya, Miguel de la
Molina, Ignacio J.
Osorio, Ana
Pineda Riu, Marta
Rueda, Daniel
Cruz, Xavier de la
Diez, Orland
Ruiz Ponte, Clara
Gutiérrez Enríquez, Sara
Vega, Ana
Lázaro García, Conxi
Keywords: Malalts de càncer
Curació de dades
Malalties hereditàries
Cancer patients
Data curation
Genetic diseases
Issue Date: 6-Dec-2020
Publisher: Walter de Gruyter
Abstract: Background: Gene panel testing by massive parallel sequencing has increased the diagnostic yield but also the number of variants of uncertain significance. Clinical interpretation of genomic data requires expertise for each gene and disease. Heterozygous ATM pathogenic variants increase the risk of cancer, particularly breast cancer. For this reason, ATM is included in most hereditary cancer panels. It is a large gene, showing a high number of variants, most of them of uncertain significance. Hence, we initiated a collaborative effort to improve and standardize variant classification for the ATM gene. Methods: Six independent laboratories collected information from 766 ATM variant carriers harboring 283 different variants. Data were submitted in a consensus template form, variant nomenclature and clinical information were curated, and monthly team conferences were established to review and adapt American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) criteria to ATM, which were used to classify 50 representative variants. Results: Amid 283 different variants, 99 appeared more than once, 35 had differences in classification among laboratories. Refinement of ACMG/AMP criteria to ATM involved specification for twenty-one criteria and adjustment of strength for fourteen others. Afterwards, 50 variants carried by 254 index cases were classified with the established framework resulting in a consensus classification for all of them and a reduction in the number of variants of uncertain significance from 58% to 42%. Conclusions: Our results highlight the relevance of data sharing and data curation by multidisciplinary experts to achieve improved variant classification that will eventually improve clinical management.
Note: Reproducció del document publicat a:
It is part of: Clinical Chemistry and Laboratory Medicine, 2020, vol. 67, num. 3, p. 518-533
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ISSN: 1434-6621
Appears in Collections:Articles publicats en revistes (Ciències Clíniques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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