Classification of germline variants identified in cancer predisposition genetic testing – consensus of the CZECANCA consortium

Česká verzia

Authors: M. Janatová ¹; Š. Chvojka ²; E. Macháčková ³; J. Soukupová ¹; P. Zemánková ^1,4; P. Nehasil ^1,4,5; T. Zavoral ⁶; L. Hrušková ⁷; K. M. Kozáková Janíková ^{8 9}; F. Lhota ²; S. Tavandzis ¹⁰; P. Kleiblová ^1,11; Z. Kleibl ¹; Czecanca Konzorcium
Authors place of work: Ústav lékařské bio chemie a laboratorní dia gnostiky, 1. LF UK a VFN v Praze ¹; Centrum lékařské genetiky a reprodukční medicíny, Gennet, Praha ²; Oddělení epidemiologie a genetiky nádorů, MOÚ Brno ³; Ústav patologické fyziologie, 1. LF UK a VFN v Praze ⁴; Klinika pediatrie a dědičných poruch metabolizmu 1. LF UK a VFN v Praze ⁵; Ústav lékařské genetiky, LF v Plzni UK a FN Plzeň ⁶; GHC Genetics, s. r. o., Praha ⁷; Ústav lékařské genetiky, LF UP a FN Olomouc ⁸; Genetická laboratoř PRONATAL, PRONATAL s. r. o., Praha ⁹; Oddělení lékařské genetiky, Laboratoře AGEL a. s., Nový Jičín ¹⁰; Ústav bio logie a lékařské genetiky, 1. LF UK a VFN v Praze ¹¹
Published in the journal: Klin Onkol 2023; 37(6): 431-439
Category: Přehled
doi: https://doi.org/10.48095/ccko2023431

Summary

Background: Hereditary cancer syndromes are an important subset of malignant cancers caused by pathogenic variants in one of many known cancer predisposition genes. Diagnosis of cancer predisposition is based on genetic testing using next-generation sequencing. This allows many genes to be analysed at once, increasing the number of variants identified. The correct classification of the variants found is essential for the clinical interpretation of genetic test results.

Purpose: The aim of this study is to summarise the rules for classifying identified variants within individual laboratories and to present the process for creating a common classification. In the Czech Republic, the sharing of identified genetic variants and the development of their consensus classification among national laboratory diagnostic communities is carried out within the Czech Cancer Panel for Clinical Application (CZECANCA) consortium of scientific and diagnostic oncogenetic laboratories. Consensus for variant classification follows a defined protocol. Sharing the results and consensus classification accelerates and refines the release of genetic test results, harmonises results between laboratories and thus contributes to improving the care of individuals at high risk of cancer and their relatives.

Keywords:

genetic testing – massively-parallel sequencing – hereditary neoplastic syndromes – clinical relevance – variant classification – national consensus

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