Clinical Implementation and Validation of Automated Human Genome Variation Society (HGVS) Nomenclature System for Next-Generation Sequencing–Based Assays for Cancer

Abstract

Human Genome Variation Society (HGVS) nomenclature is a de facto clinical standard for reporting DNA sequence variants. With increasing use of high-throughput sequencing, manual generation of HGVS nomenclatures for all variants is impractical and error-prone. It is therefore beneficial to include one or more HGVS generator tools in next-generation sequencing (NGS) bioinformatics pipelines to enable automated, consistent, and accurate generation of HGVS nomenclature after appropriate validation. The authors implemented an HGVS nomenclature tool, the hgvs package, by integrating it into their custom-developed NGS variant management and reporting software. Use of Docker containers provided a strategic advantage to the integration process. Clinical implementation of the hgvs package was validated using a cohort of 330 variants that appropriately represented cancer-related genes and clinically important variant types. The hgvs package was able to generate HGVS-compliant variant nomenclature (both c. and p.) for 308 of the 330 (93.3%) variants, including all those in the coding and untranslated regions, and 32 of 35 (91.4%) in the consensus splice site region. Discrepant HGVS nomenclature involved variants in the intronic (16 of 40) and consensus splice site (3 of 35) regions with repeat sequences. Overall, implementation of the hgvs package in the clinical NGS workflow improved consistency and accuracy of reporting HGVS nomenclature.

Consistency and reproducibility of next‐generation sequencing in cytopathology: A second worldwide ring trial study on improved cytological molecular reference specimens

“…After validation by AccuRef Diagnostics, the sets of unstained slides (A‐D) were distributed to the 17 laboratories; some of the laboratories that specialized in NGS testing of cytological samples had also taken part in the working group of the latest annual meeting on molecular cytopathology held in Naples, Italy (Fig. ) . Each laboratory stained the slides by applying their own routine protocols (Diff Quik, Papanicolaou, or hematoxylin‐eosin staining).…”

A new hybrid record linkage process to make epidemiological databases interoperable: application to the GEMO and GENEPSO studies involving BRCA1 and BRCA2 mutation carriers

“…Record linkage is highly sensitive to data quality. Therefore, we performed data cleaning and standardization [21][22][23], such as removing duplicates, deleting spaces in strings, standardizing the format of matching and blocking variables, converting mutation descriptions to standard Human Genome Variation Society (HGVS) nomenclature [24], standardizing recruiting center number (CTR), and splitting dates of birth into month, day and year in order to compare respectively each of them and give credit for partial agreement.…”

A new hybrid record linkage process to render epidemiological databases interoperable: application to the GEMO and GENEPSO studies involving BRCA1 and BRCA2 mutation carriers

“…Record linkage is highly sensitive to data quality. Therefore, we performed data cleaning and standardization [21][22][23], such as removing duplicates, deleting spaces in strings, standardizing format of linkage variables, converting mutation descriptions to standard Human Genome Variation Society (HGVS) nomenclature [24], and splitting dates of birth into month, day and year in order to compare respectively each of them and give credit for partial agreement.…”