EXTERNAL QUALITY ASSESSMENT
relevant variants for a full ACMG variant classification. Therefore, participants were being timed while assessing the annotated variants and had to choose to ‘exclude from analysis’, ‘definitely report’ or ‘needs further variant classification’. All participants had to complete each case in one sitting. The pilot assessment for WGS/WES proportionate variant analysis demonstrated a global uptake with 133 participants from 30 different countries. Overall, 55% of participants were laboratory scientists.
Of the six clinical cases provided to participants, three had no genetic cause identified and three had reportable likely pathogenic/pathogenic variants. Overall, 16.1% of responses were not as expected; however, there was a significant overlap with the ‘needs further variant classification’ response7
(Table 1).
As participants were timed for this assessment, a broad range of times taken per case was observed. As it is shown in Figure 6, 35% of participants analysed the cases in less than hour; this figure was lower for one of the cases; case 2, which included the highest number of variants. 47% of participants did not complete a case within one session, therefore their times could not be benchmarked. From this pilot assessment it was shown that many participants did not assess allele depth to check low coverage or skewed reads which may indicate putative sequencing artefacts. Participants also reported more variants of uncertain clinical significance (VUS) in cases where no causative variants were identified. Additionally, some participants reported all VUS including low VUS with limited evidence for pathogenicity, likely due to regional differences in reporting practice. Several participants reported all VUS in cases where a causative variant had also been identified. Finally, variable reporting of low penetrance incidental finding was observed.
All GENie modules, except for BRCA1,
BRCA2 and other HRR gene variant classification (BRCA run) assessments and WGS/WES proportionate variant analysis, are able to offer real-time feedback and participants can compare their submission to the expected answers provided by expert advisors. Participants can now earn one CPD/CME hour for every completed module.
Summary
In the last two years, the GENie platform has been a promising solution for supporting variant classification and nomenclature interpretation practices which is already used by thousands of
48 0 0 Case 1 less than 30 minutes between 1 hour and 2 hours Fig 6. Times taken per case.
individuals. By using GENie, individuals can gain the necessary knowledge and skills, which will help them to maintain their competency. The growing uptake of the GENie platform indicates a clear demand for continued education, and the outcomes further reveal significant variability in competency levels. It is expected that the use of GENie will continuously grow as it is CPD/CME certified.
References 1 HGVS Variant Nomenclature Committee.
HGVS Nomenclature. (Human Genome Variation Society, 2025).
https://hgvs-nomenclature.org/
2 McGowan-Jordan J, Hastings RJ, Moore S, eds. ICSN 2020: An International System for Human Cytogenomic Nomenclature (2020) Reprint of ‘Cytogenetic and Genome Research 2020, Vol. 160, No. 7-8’. Karger. 2020. doi:10.1159/isbn.978-3- 318-06867-2
3 Hastings RJ, Moore S, Chia N, eds. ISCN 2024: An International System for Human Cytogenomic Nomenclature. Karger. 2024. doi: 10.1159/isbn.978-3-318-07331-7
4 Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424. doi:10.1038/gim.2015.30
5 Riggs ER, Andersen EF, Cherry AM, et al. Technical standards for the interpretation
and reporting of constitutional copy- number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020;22(2):245-257. doi:10.1038/s41436- 019-0686-8
6 Ellard S, Morgan S, Wynn SL, et al. Rare disease genomic testing in the UK and Ireland: promoting timely and equitable access. J Med Genet. 2024;61(12):1103- 1112. doi:10.1136/jmg-2024-110228
7 Durkie M, Kolozi A, Stals K, et al. Individual competence assessment of WGS/WES proportionate variant analysis using the GENie platform. Poster presented at: European Human Genetics Conference; 24-27 May 2025; Milan, Italy.
https://genqa.org/includes/items/ publications/2548_eshg-genie-pva-2025. pdf
Angie Kolozi is a Genetic Technologist and GENie Lead at GenQA.
GenQA prides itself on being the sole genomics EQA provider to cover the entire clinical genomics service, from patient counselling, sample preparation, testing processes, results interpretation and reporting. At GenQA, laboratories and individual clinicians have access to more than 100 unique EQAs; available for a range of rare and inherited disorders and acquired disease and prepared in GenQA’s purpose-built genomic laboratory.
https://genqa.org/ DECEMBER 2025
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