Clinically actionable secondary findings in 130 triads from sub-Saharan African families with non-syndromic orofacial clefts

Abimbola Oladayo, Lord Jephthah Joojo Gowans, Waheed Awotoye, Azeez Alade, Tamara Busch, Thirona Naicker, Mekonen A. Eshete, Wasiu L. Adeyemo, Jacqueline B. Hetmanski, Erliang Zeng, Olawale Adamson, Chinyere Adeleke, Mary Li, Veronica Sule, Sami Kayali, Joy Olotu, Peter A. Mossey, Solomon Obiri-Yeboah, Carmen J. Buxo, Terri BeatyMargaret Taub, Peter Donkor, Mary L. Marazita, Oluwakemi Odukoya, Adebowale A. Adeyemo, Jeffrey C. Murray, Anya Prince, Azeez Butali (Lead / Corresponding author)

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Introduction: The frequency and implications of secondary findings (SFs) from genomic testing data have been extensively researched. However, little is known about the frequency or reporting of SFs in Africans, who are underrepresented in large-scale population genomic studies. The availability of data from the first whole-genome sequencing for orofacial clefts in an African population motivated this investigation.

Methods: In total, 130 case-parent trios were analyzed for SFs within the ACMG SFv.3.0 list genes. Additionally, we filtered for four more genes (HBB, HSD32B, G6PD and ACADM).

Results: We identified 246 unique variants in 55 genes; five variants in four genes were classified as pathogenic or likely pathogenic (P/LP). The P/LP variants were seen in 2.3% (9/390) of the subjects, a frequency higher than ~1% reported for diverse ethnicities. On the ACMG list, pathogenic variants were observed in PRKAG (p. Glu183Lys). Variants in the PALB2 (p. Glu159Ter), RYR1 (p. Arg2163Leu) and LDLR (p. Asn564Ser) genes were predicted to be LP.

Conclusion: This study provides information on the frequency and pathogenicity of SFs in an African cohort. Early risk detection will help reduce disease burden and contribute to efforts to increase knowledge of the distribution and impact of actionable genomic variants in diverse populations.

Original languageEnglish
Article numbere2237
Number of pages13
JournalMolecular Genetics and Genomic Medicine
Issue number10
Early online date26 Jul 2023
Publication statusPublished - Oct 2023


  • ACMG guideline
  • orofacial clefts
  • secondary findings
  • sub-Saharan Africa
  • whole genome sequencing


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