April 17, 2024

Focus on – Geneyx Cohort search and NonCoding regions

Yuyang Chen, Ruebena Dawes, Hyung Chul Kim. Read more below.

Published Authors: Yuyang Chen, Ruebena Dawes, Hyung Chul Kim, Sarah L Stenton, Susan Walker, Alicia Ljungdahl, Jenny Lord, Vijay S Ganesh, Jialan Ma, Alexandra C Martin-Geary, Gabrielle Lemire, Elston N D’Souza, Shan Dong, Jamie M Ellingford, David R Adams, Kirsten Allan, Madhura Bakshi, Erin E Baldwin, Seth I Berger,Jonathan A Bernstein, Natasha J Brown, Lindsay C Burrage, Kimberly Chapman, Alison G Compton, Chloe A Cunningham, Precilla D’Souza, Emmanuèle C Délot, Kerith-Rae Dias, Ellen R Elias, Carey-Anne Evans, Lisa Ewans, Kimberly Ezell, Jamie L Fraser, Lyndon Gallacher, Casie A Genetti, Christina L Grant, Tobias Haack, Alma Kuechler, Seema R Lalani, Elsa Leitão, Anna Le Fevre,Richard J Leventer, Jan E Liebelt, Paul J Lockhart, Alan S Ma, Ellen F Macnamara, Taylor M Maurer, Hector R Mendez, Stephen B Montgomery, Marie-Cécile Nassogne, Serena Neumann, Melanie O’Leary, Elizabeth E Palmer, John Phillips, Georgia Pitsava, Ryan Pysar, Heidi L Rehm, Chloe M Reuter, Nicole Revencu, Angelika Riess, Rocio Rius, Lance Rodan, Tony Roscioli, Jill A Rosenfeld, Rani Sachdev, Cas Simons, Sanjay M Sisodiya, Penny Snell, Laura St Clair, Zornitza Stark, Tiong Yang Tan, Natalie B Tan, Suzanna EL Temple, David R Thorburn, Cynthia J Tifft, Eloise Uebergang, Grace E VanNoy, Eric Vilain, David H Viskochil, Laura Wedd, Matthew T Wheeler, Susan M White, Monica Wojcik, Lynne A Wolfe, Zoe Wolfenson, Changrui Xiao, David Zocche, John L Rubenstein, Eirene Markenscoff-Papadimitriou, Sebastian M Fica, Diana Baralle, Christel Depienne, Daniel G MacArthur, Joanna MM Howson, Stephan J Sanders, Anne O’Donnell-Luria, Nicola Whiffin

Summarized by: Dr. Suzanne Claire Drury


On April 8th 2024, Chen et al published the identification of variants in a non-coding RNA (RNU4-2) which remarkably explained the diagnosis of approximately ~0.5% of all undiagnosed individuals with neurodevelopmental disorders (NDD). The authors initially identified a recurrent variant (GRCh38:chr12:120,291,839:T:TA; n.64_65insT) in 46 individuals in the Genomics England (GEL) cohort. The variant was not found in any other GEL cohorts (NDD with an existing genetic diagnosis, non-NDD cases, or unaffected individuals). The authors further investigated the phenotypes of Individuals with the variant and showed that there was an enrichment of developmental delay, delayed gross motor development, microcephaly, delayed fine motor development hypotonia, short stature, drooling and absent speech. Expanding analysis to a highly constrained 18bp region of the gene (chr12:120,291,825-120,291,842) and additional NDD cohorts identified a total of 119 individuals with variants in this region, 77.3% of which have n.64_65insT. This variant was observed once in the UK Biobank, in an individual with ‘personal history of disease of the nervous stem and sense organs’. 


Using the Geneyx Analysis platform doctors from Hadassah Medical Centre were able to easily search their cohort of 365 genomes to identify a case with this variant, taking only 0.5 minutes and less than a day after the paper was published. The case had phenotype intellectual disability, seizures, and microcephaly and was previously undiagnosed.  


The ‘Variant Browser feature of Geneyx Analysis, enables users to search via a graphical user interface for specific regions across their cohort of data, without relying on the skills of a bioinformatician. This can expedite case identification and resolution of unsolved cases.  

The Geneyx Analysis CE-IVD platform has several other features to support users make the most of genome sequencing, including in non-coding regions. 


Smart filter – include all variants in the genome at a defined frequency and CADD score, regardless of whether in a coding region.  

Modifier – capture in your analysis all regulatory elements outside of coding regions. It ensures that elements, such as enhancers or promoters, are considered during the analysis. 

Focused analysis – generate a sub-analysis, for example focused only on non-coding regions, to stratify your workflow 

Benefit from enhancers scores such as  

Enhancers (ENHS): The number of enhancers impacted by the event. 

ENH SCORE: Enhancer confidence score. 

ENH-GENE SCORE: Gene-Enhancer associated score. 


To find out more about these and many other features contact us today for your introduction and demonstration.  




  1. https://www.medrxiv.org/content/10.1101/2024.04.07.24305438v2 

View additional Publications:

Variant Co-occurrence Counts by Gene in gnomAD




Selected Videos

Geneyx Analysis Version 5.12 Release


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