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Variant Selection and Interpretation: An Example of Modified VarSome Classifier of ACMG Guidelines in the Diagnostic Setting
Variant interpretation is challenging as it involves combining different levels of evidence in order to evaluate the role of a specific variant in the context of a patient’s disease. Many in-depth refinements followed the original 2015 American College of Medical Genetics (ACMG) guidelines to overco...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700904/ https://www.ncbi.nlm.nih.gov/pubmed/34946832 http://dx.doi.org/10.3390/genes12121885 |
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author | Cristofoli, Francesca Sorrentino, Elisa Guerri, Giulia Miotto, Roberta Romanelli, Roberta Zulian, Alessandra Cecchin, Stefano Paolacci, Stefano Miertus, Jan Bertelli, Matteo Maltese, Paolo Enrico Chiurazzi, Pietro Stuppia, Liborio Castori, Marco Marceddu, Giuseppe |
author_facet | Cristofoli, Francesca Sorrentino, Elisa Guerri, Giulia Miotto, Roberta Romanelli, Roberta Zulian, Alessandra Cecchin, Stefano Paolacci, Stefano Miertus, Jan Bertelli, Matteo Maltese, Paolo Enrico Chiurazzi, Pietro Stuppia, Liborio Castori, Marco Marceddu, Giuseppe |
author_sort | Cristofoli, Francesca |
collection | PubMed |
description | Variant interpretation is challenging as it involves combining different levels of evidence in order to evaluate the role of a specific variant in the context of a patient’s disease. Many in-depth refinements followed the original 2015 American College of Medical Genetics (ACMG) guidelines to overcome subjective interpretation of criteria and classification inconsistencies. Here, we developed an ACMG-based classifier that retrieves information for variant interpretation from the VarSome Stable-API environment and allows molecular geneticists involved in clinical reporting to introduce the necessary changes to criterion strength and to add or exclude criteria assigned automatically, ultimately leading to the final variant classification. We also developed a modified ACMG checklist to assist molecular geneticists in adjusting criterion strength and in adding literature-retrieved or patient-specific information, when available. The proposed classifier is an example of integration of automation and human expertise in variant curation, while maintaining the laboratory analytical workflow and the established bioinformatics pipeline. |
format | Online Article Text |
id | pubmed-8700904 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87009042021-12-24 Variant Selection and Interpretation: An Example of Modified VarSome Classifier of ACMG Guidelines in the Diagnostic Setting Cristofoli, Francesca Sorrentino, Elisa Guerri, Giulia Miotto, Roberta Romanelli, Roberta Zulian, Alessandra Cecchin, Stefano Paolacci, Stefano Miertus, Jan Bertelli, Matteo Maltese, Paolo Enrico Chiurazzi, Pietro Stuppia, Liborio Castori, Marco Marceddu, Giuseppe Genes (Basel) Communication Variant interpretation is challenging as it involves combining different levels of evidence in order to evaluate the role of a specific variant in the context of a patient’s disease. Many in-depth refinements followed the original 2015 American College of Medical Genetics (ACMG) guidelines to overcome subjective interpretation of criteria and classification inconsistencies. Here, we developed an ACMG-based classifier that retrieves information for variant interpretation from the VarSome Stable-API environment and allows molecular geneticists involved in clinical reporting to introduce the necessary changes to criterion strength and to add or exclude criteria assigned automatically, ultimately leading to the final variant classification. We also developed a modified ACMG checklist to assist molecular geneticists in adjusting criterion strength and in adding literature-retrieved or patient-specific information, when available. The proposed classifier is an example of integration of automation and human expertise in variant curation, while maintaining the laboratory analytical workflow and the established bioinformatics pipeline. MDPI 2021-11-25 /pmc/articles/PMC8700904/ /pubmed/34946832 http://dx.doi.org/10.3390/genes12121885 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Communication Cristofoli, Francesca Sorrentino, Elisa Guerri, Giulia Miotto, Roberta Romanelli, Roberta Zulian, Alessandra Cecchin, Stefano Paolacci, Stefano Miertus, Jan Bertelli, Matteo Maltese, Paolo Enrico Chiurazzi, Pietro Stuppia, Liborio Castori, Marco Marceddu, Giuseppe Variant Selection and Interpretation: An Example of Modified VarSome Classifier of ACMG Guidelines in the Diagnostic Setting |
title | Variant Selection and Interpretation: An Example of Modified VarSome Classifier of ACMG Guidelines in the Diagnostic Setting |
title_full | Variant Selection and Interpretation: An Example of Modified VarSome Classifier of ACMG Guidelines in the Diagnostic Setting |
title_fullStr | Variant Selection and Interpretation: An Example of Modified VarSome Classifier of ACMG Guidelines in the Diagnostic Setting |
title_full_unstemmed | Variant Selection and Interpretation: An Example of Modified VarSome Classifier of ACMG Guidelines in the Diagnostic Setting |
title_short | Variant Selection and Interpretation: An Example of Modified VarSome Classifier of ACMG Guidelines in the Diagnostic Setting |
title_sort | variant selection and interpretation: an example of modified varsome classifier of acmg guidelines in the diagnostic setting |
topic | Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8700904/ https://www.ncbi.nlm.nih.gov/pubmed/34946832 http://dx.doi.org/10.3390/genes12121885 |
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