Variant curation and interpretation in hereditary cancer genes : An institutional experience in Latin America
© 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC..
BACKGROUND: Variant curation refers to the application of evidence-based methods for the interpretation of genetic variants. Significant variability in this process among laboratories affects clinical practice. For admixed Hispanic/Latino populations, underrepresented in genomic databases, the interpretation of genetic variants for cancer risk is challenging.
METHODS: We retrospectively evaluated 601 sequence variants detected in patients participating in the largest Institutional Hereditary Cancer Program in Colombia. VarSome and PathoMAN were used for automated curation, and ACMG/AMP and Sherloc criteria were applied for manual curation.
RESULTS: Regarding the automated curation, 11% of the variants (64/601) were reclassified, 59% (354/601) had no changes in its interpretation, and the other 30% (183/601) presented conflicting interpretations. With respect to manual curation, of the 183 variants with conflicting interpretations, 17% (N = 31) were reclassified, 66% (N = 120) had no changes in their initial interpretation, and 17% (N = 32) remained with conflicting interpretation status. Overall, 91% of the VUS were downgraded and 9% were upgraded.
CONCLUSIONS: Most VUS were reclassified as benign/likely benign. Since false-positive and -negative results can be obtained with automated tools, manual curation should also be used as a complement. Our results contribute to improving cancer risk assessment and management for a broad range of hereditary cancer syndromes in Hispanic/Latino populations.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:11 |
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| Enthalten in: |
Molecular genetics & genomic medicine - 11(2023), 5 vom: 18. Mai, Seite e2141 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Manotas, María Carolina [VerfasserIn] |
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| Links: |
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| Themen: |
Automated curation |
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| Anmerkungen: |
Date Completed 15.05.2023 Date Revised 15.05.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/mgg3.2141 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM354107666 |
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| 245 | 1 | 0 | |a Variant curation and interpretation in hereditary cancer genes |b An institutional experience in Latin America |
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| 500 | |a Date Revised 15.05.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC. | ||
| 520 | |a BACKGROUND: Variant curation refers to the application of evidence-based methods for the interpretation of genetic variants. Significant variability in this process among laboratories affects clinical practice. For admixed Hispanic/Latino populations, underrepresented in genomic databases, the interpretation of genetic variants for cancer risk is challenging | ||
| 520 | |a METHODS: We retrospectively evaluated 601 sequence variants detected in patients participating in the largest Institutional Hereditary Cancer Program in Colombia. VarSome and PathoMAN were used for automated curation, and ACMG/AMP and Sherloc criteria were applied for manual curation | ||
| 520 | |a RESULTS: Regarding the automated curation, 11% of the variants (64/601) were reclassified, 59% (354/601) had no changes in its interpretation, and the other 30% (183/601) presented conflicting interpretations. With respect to manual curation, of the 183 variants with conflicting interpretations, 17% (N = 31) were reclassified, 66% (N = 120) had no changes in their initial interpretation, and 17% (N = 32) remained with conflicting interpretation status. Overall, 91% of the VUS were downgraded and 9% were upgraded | ||
| 520 | |a CONCLUSIONS: Most VUS were reclassified as benign/likely benign. Since false-positive and -negative results can be obtained with automated tools, manual curation should also be used as a complement. Our results contribute to improving cancer risk assessment and management for a broad range of hereditary cancer syndromes in Hispanic/Latino populations | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a automated curation | |
| 650 | 4 | |a hereditary cancer | |
| 650 | 4 | |a manual curation | |
| 650 | 4 | |a variant interpretation | |
| 700 | 1 | |a Rivera, Ana Lucia |e verfasserin |4 aut | |
| 700 | 1 | |a Sanabria-Salas, María Carolina |e verfasserin |4 aut | |
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