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Human Genetics

, Volume 137, Issue 1, pp 31–37 | Cite as

Actionable secondary findings from whole-genome sequencing of 954 East Asians

  • Clara Sze-man TangEmail author
  • Saloni Dattani
  • Man-ting So
  • Stacey S. Cherny
  • Paul K. H. Tam
  • Pak C. Sham
  • Maria-Mercè Garcia-BarceloEmail author
Original Investigation

Abstract

Recently, the American College of Medical Genetics (ACMG) recommended the return of actionable secondary findings detected from clinical sequencing. The reported frequency of secondary findings in Asian populations were highly variable and it is unclear whether the uniformity in coverage offered by whole-genome sequencing (WGS) may impact the estimate. In this analysis, we aimed to refine the rate of secondary findings on East Asians through a large-scale WGS study. We classified 1256 protein-altering or splicing variants of the 59 actionable genes detected from WGS of 954 East Asians in strict accordance with the ACMG and the Association for Molecular Pathology guidelines. A total of 21 pathogenic or likely pathogenic variants were detected in 24 of the 954 East Asian genomes with an estimate of 2.5% of East Asians carrying actionable variants. Although the overall estimate of secondary findings was consistent with those reported for non-East Asian ethnicities, genetic and allelic heterogeneity was observed. WGS offers a wider breadth of coverage over WES, which highlights the need to further investigate the variable sensitivity of WES and WGS in the detection of secondary findings. Identifying secondary findings in populations underrepresented in previous genetic literature might improve variant interpretation and has a profound impact on local decision-making with regard to the cost-effectiveness of returning the secondary findings from clinical sequencing.

Notes

Acknowledgements

This work was supported by: Theme-based Research scheme T12C-714/14-R to P.T., Human Medical Research Fund (HMRF) 02131866 and 01121516 to M.M.G.B and 0451966 to C.S.T. and Seed Fund for Basic Research of The University of Hong Kong 201606159005 to C.S.T.

Compliance with ethical standards

Conflict of interest

We declare no conflict of interest.

Supplementary material

439_2017_1852_MOESM1_ESM.xlsx (16 kb)
Supplementary material 1 (XLSX 16 kb)
439_2017_1852_MOESM2_ESM.docx (159 kb)
Supplementary material 2 (DOCX 158 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Division of Paediatric Surgery, Department of Surgery, Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina
  2. 2.Dr. Li Dak-Sum Research CentreThe University of Hong Kong-Karolinska Institutet Collaboration in Regenerative MedicineHong KongChina
  3. 3.Department of Psychiatry, Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina
  4. 4.Institute of Psychiatry, Psychology and NeuroscienceKing’s College LondonLondonUK
  5. 5.Centre for Genomic Sciences, Li Ka Shing Faculty of MedicineThe University of Hong KongHong KongChina
  6. 6.Department of Epidemiology and Preventive Medicine and Department of Anatomy and AnthropologyTel Aviv UniversityTel AvivIsrael
  7. 7.State Key Laboratory of Brain and Cognitive SciencesThe University of Hong KongHong KongChina

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