Variant Curation

Variant curation is the process of gathering and analyzing evidence to classify genetic variants as benign, pathogenic or a variant of uncertain significance (VUS). It’s an essential part of genomic medicine, transforming raw sequence data into meaningful insights. At COIN, variant curation plays an important role in identifying the genetic architecture of neurological disorders, particularly those affecting African patients who have historically been underrepresented in genomic research.  

In practice, variant curation involves gathering and integrating multiple pieces of evidence: how common a variant is across different populations, whether it affects protein function in the body, if it has been previously documented in databases (see data sharing), and whether it aligns with the patient’s clinical presentation. Variant scientists apply internationally accepted standards, such as the ACMG-AMP guidelines, while also considering regionally relevant data that might influence how evidence is interpreted.

Why This Work Matters  

Variant curation is becoming increasingly advanced with advancing technologies and the sharing of data and collaborative efforts globally. However, African genomes remain underrepresented in datasets, leading to higher rates of VUS’s among African patients. Without region-specific data, many variants cannot be confidently classified, leaving gaps in diagnosis and care.

Some of the key challenges include, limited population reference data, underrepresentation of African variants in global repositories and the need for training and infrastructure to support expert curation locally. COIN addresses these gaps by integrating clinical data and bioinformatic pipelines from African-trained professionals. This multidisciplinary approach ensures that each variant is not only technically reviewed but clinically and ethically contextualized.

Furthermore, by focusing on African-led curation, our work highlights how regional allele frequencies and submissions to global databases like ClinVar can make variant classification more accurate and equitable. This approach hopes to increase the diagnostic testing and yield for neurological disorders but also ensures that African data and expertise are shaping the landscape of rare diseases worldwide.  

Resources, Tools, or Databases  

Our variant curation work draws on both global and regional resources to ensure accurate, contextually relevant classifications. We routinely use tools such as Franklin, ClinVar, gnomAD alongside the African Genome Variation Database to interpret variants.  

We contribute to the growing body of African genomic data through ClinVar and our publications, including those by Nel et al. 2022.  

Looking Ahead

Our goal is to ensure African genomic variation is accurately interpreted and globally represented. Each variant we curate represents a step towards improving diagnosis accuracy for African patients, strengthening data quality and contributing to international knowledge-sharing platforms.