ConsCal: A tool to aid medical genetics professionals in consanguineous populations

Abstract

AbstractConsanguineous populations have a higher frequency of autosomal recessive diseases when compared to the rest of the world. This frequency is high enough that families in these populations may even have multiple autosomal recessive diseases. The recurrence risk calculation for the various combinations becomes increasingly more difficult as more recessive diseases are encountered in a family. Another challenge in these populations is investigating the pathogenicity of a variant by considering its segregation with the phenotype. Consanguinity causes the appearance of many homozygous variants due to the identity by descent phenomenon. As the number of these variants increases, so does the percentage of novel variants that need to be classified using segregation. Furthermore, the complexity of calculating the segregation power increases with the level of inbreeding, and in the case of consanguineous families, their pedigrees tend to be very complex. With the aim of addressing these two challenges using a mathematical algorithm, ConsCal, a tool made to specifically cater to medical genetics professionals working with consanguineous populations, was developed. The user‐friendly tool contains two primary functions. It simplifies recurrence risk calculations for any combination of autosomal recessive diseases and analyzes familial segregation data to assign a numerical value to the segregation power of a given variant to aid in its classification. As the use of genomics becomes more widespread, this tool can help address the growing need in calculating recurrence risk and segregation power in consanguineous populations.