Comparison of the ABC and ACMG systems for variant classification
Gunnar Houge
(1)
,
Eirik Bratland
(1)
,
Ingvild Aukrust
(1)
,
Kristian Tveten
,
Gabrielė Žukauskaitė
(2)
,
Ivona Sansovic
(3)
,
Alejandro J. Brea-Fernández
(4)
,
Karin Mayer
,
Teija Paakkola
,
Caoimhe Mckenna
,
William Wright
,
Milica Keckarevic Markovic
(5)
,
Dorte L. Lildballe
(6)
,
Michal Konecny
(7)
,
Thomas Smol
(8, 9)
,
Pia Alhopuro
(10)
,
Estelle Arnaud Gouttenoire
,
Katharina Obeid
(11)
,
Albena Todorova
,
Milena Jankovic
(5)
,
Joanna M. Lubieniecka
(12)
,
Maja Stojiljkovic
(5)
,
Marie-Pierre Buisine
(13, 14)
,
Bjørn Ivar Haukanes
(1)
,
Marie Lorans
(6)
,
Hanno Roomere
(15)
,
François M. Petit
(16)
,
Maria K. Haanpää
(17)
,
Claire Beneteau
(18)
,
Belén Pérez
(19)
,
Dijana Plaseska-Karanfilska
(20)
,
Matthias Rath
(21, 22)
,
Nico Fuhrmann
(23)
,
Bibiana I. Ferreira
(24)
,
Coralea Stephanou
(25)
,
Wenche Sjursen
(26)
,
Aleš Maver
(27)
,
Cécile Rouzier
(28, 29, 30)
,
Adela Chirita-Emandi
(31)
,
João Gonçalves
(32)
,
Wei Cheng David Kuek
(33)
,
Martin Broly
(34)
,
Lonneke Haer-Wigman
(35)
,
Meow-Keong Thong
(36)
,
Sok-Kun Tae
(37)
,
Michaela Hyblova
(38)
,
Johan T. den Dunnen
(39)
,
Andreas Laner
1
Haukeland University Hospital
2 Vilnius University [Vilnius]
3 University of Zagreb
4 CIBER de Enfermedades Raras (CIBERER)
5 University of Belgrade [Belgrade]
6 Aarhus University Hospital
7 Trnava University
8 Institut de génétique médicale
9 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
10 HUS - Helsinki University Hospital [Finland]
11 Heidelberg University Hospital [Heidelberg]
12 RUB - Ruhr University Bochum = Ruhr-Universität Bochum
13 Institut de Biochimie et Biologie Moléculaire [CHRU Lille]
14 CANTHER - Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
15 University of Tartu
16 UNICANCER/CAL - Centre de Lutte contre le Cancer Antoine Lacassagne [Nice]
17 University of Turku
18 CHU Bordeaux
19 UAM - Universidad Autónoma de Madrid
20 MASA - Macedonian Academy of Sciences and Arts [Skopje, North Macedonia]
21 Universität Greifswald - University of Greifswald
22 Medical School Hamburg
23 University of Cologne
24 University of Algarve [Portugal]
25 Cyprus Institute of Neurology and Genetics
26 St. Olav's University Hospital - St. Olavs Hospital HF
27 UMCL - University Medical Centre Ljubljana [Ljubljana, Slovenia]
28 CHU Nice - Centre Hospitalier Universitaire de Nice
29 UniCA - Université Côte d'Azur
30 IRCAN - Institut de Recherche sur le Cancer et le Vieillissement
31 UMFT - Victor Babeş University of Medicine and Pharmacy
32 INSA - Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal]
33 NUH - National University Hospital [Singapore]
34 University Hospital of Montpellier
35 Radboud University Medical Center [Nijmegen]
36 UM - University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie]
37 Faculty of Medicine, University of Malaya [Kuala Lumpur, Malaisie]
38 SMU - Slovak Medical University of Bratislava
39 LUMC - Leiden University Medical Center
2 Vilnius University [Vilnius]
3 University of Zagreb
4 CIBER de Enfermedades Raras (CIBERER)
5 University of Belgrade [Belgrade]
6 Aarhus University Hospital
7 Trnava University
8 Institut de génétique médicale
9 CHRU Lille - Centre Hospitalier Régional Universitaire [CHU Lille]
10 HUS - Helsinki University Hospital [Finland]
11 Heidelberg University Hospital [Heidelberg]
12 RUB - Ruhr University Bochum = Ruhr-Universität Bochum
13 Institut de Biochimie et Biologie Moléculaire [CHRU Lille]
14 CANTHER - Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277
15 University of Tartu
16 UNICANCER/CAL - Centre de Lutte contre le Cancer Antoine Lacassagne [Nice]
17 University of Turku
18 CHU Bordeaux
19 UAM - Universidad Autónoma de Madrid
20 MASA - Macedonian Academy of Sciences and Arts [Skopje, North Macedonia]
21 Universität Greifswald - University of Greifswald
22 Medical School Hamburg
23 University of Cologne
24 University of Algarve [Portugal]
25 Cyprus Institute of Neurology and Genetics
26 St. Olav's University Hospital - St. Olavs Hospital HF
27 UMCL - University Medical Centre Ljubljana [Ljubljana, Slovenia]
28 CHU Nice - Centre Hospitalier Universitaire de Nice
29 UniCA - Université Côte d'Azur
30 IRCAN - Institut de Recherche sur le Cancer et le Vieillissement
31 UMFT - Victor Babeş University of Medicine and Pharmacy
32 INSA - Instituto Nacional de Saùde Dr Ricardo Jorge [Portugal]
33 NUH - National University Hospital [Singapore]
34 University Hospital of Montpellier
35 Radboud University Medical Center [Nijmegen]
36 UM - University of Malaya = Universiti Malaya [Kuala Lumpur, Malaisie]
37 Faculty of Medicine, University of Malaya [Kuala Lumpur, Malaisie]
38 SMU - Slovak Medical University of Bratislava
39 LUMC - Leiden University Medical Center
Kristian Tveten
- Fonction : Auteur
Karin Mayer
- Fonction : Auteur
Teija Paakkola
- Fonction : Auteur
Caoimhe Mckenna
- Fonction : Auteur
William Wright
- Fonction : Auteur
Estelle Arnaud Gouttenoire
- Fonction : Auteur
Albena Todorova
- Fonction : Auteur
Andreas Laner
- Fonction : Auteur
Résumé
The ABC and ACMG variant classification systems were compared by asking mainly European clinical laboratories to classify variants in 10 challenging cases using both systems, and to state if the variant in question would be reported as a relevant result or not as a measure of clinical utility. In contrast to the ABC system, the ACMG system was not made to guide variant reporting but to determine the likelihood of pathogenicity. Nevertheless, this comparison is justified since the ACMG class determines variant reporting in many laboratories. Forty-three laboratories participated in the survey. In seven cases, the classification system used did not influence the reporting likelihood when variants labeled as “maybe report” after ACMG-based classification were included. In three cases of population frequent but disease-associated variants, there was a difference in favor of reporting after ABC classification. A possible reason is that ABC step C (standard variant comments) allows a variant to be reported in one clinical setting but not another, e.g., based on Bayesian-based likelihood calculation of clinical relevance. Finally, the selection of ACMG criteria was compared between 36 laboratories. When excluding criteria used by less than four laboratories (<10%), the average concordance rate was 46%. Taken together, ABC-based classification is more clear-cut than ACMG-based classification since molecular and clinical information is handled separately, and variant reporting can be adapted to the clinical question and phenotype. Furthermore, variants do not get a clinically inappropriate label, like pathogenic when not pathogenic in a clinical context, or variant of unknown significance when the significance is known.
| Origine | Publication financée par une institution |
|---|
