A population-based resource for the prioritization of rare variants of unknown significance in clinical genomics

In the Saguenay-Lac-Saint-Jean founder population, 131 founder variants of interest were identified, and most would likely be missed by conventional annotation-based approaches.

• Why it matters: Many rare-disease causal variants remain undiscovered, and existing clinical annotations can leave potentially pathogenic variants unprioritized or unrecognized.
• What they did: Whole-genome sequencing data were analyzed to find enriched rare variants and assess founder status via identity-by-descent sharing, then variant impact was scored using functional prediction tools without using prior clinical classifications.
• The result: A web-based platform was built to deliver up-to-date interpretations for clinician-selected variants, showing that potentially pathogenic variants can remain undetected even in extensively studied founder populations.

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