2026-04-17T07:57:57Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1762672025-11-20T15:57:20Zcom_2072_1057col_2072_478798col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Feliubadaló i Elorza, Maria Lídia author Moles Fernández, Alejandro author Santamariña-Pena, Marta author Sánchez, Alysson T. author López Novo, Anael author Porras, Luz Marina author Blanco, Ana author Capellá, G. (Gabriel) author Hoya, Miguel de la author Molina, Ignacio J. author Osorio, Ana author Pineda Riu, Marta author Rueda, Daniel author Cruz, Xavier de la author Diez, Orland author Ruiz Ponte, Clara author Gutiérrez Enríquez, Sara author Vega, Ana author Lázaro García, Conxi author 2021-04-13T11:10:47Z 2021-12-06T06:10:20Z 2020-12-06 2021-04-13T11:10:47Z 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. Malalts de càncer Espanya Curació de dades Malalties hereditàries Cancer patients Spain Data curation Genetic diseases A Collaborative Effort to Define Classification Criteria for ATM Variants in Hereditary Cancer Patients