Purpose: The aim of the study was to compare the data for mutations related to clinical disorders reported among Ashkenazi Jewish patients in the Israeli National Genetic Database (INGD) with variants included in the Genome Aggregation Database (gnomAD).
Methods: We extracted data for mutations claimed to cause disorders reported among Ashkenazi Jews from the INGD and searched gnomAD for each of them. We compared the allele frequency of each variant in Ashkenazi Jews with that of other delineated populations.
Results: Of the 58 INGD-reported mutations related to autosomal-dominant disorders, 19 were present in gnomAD (32.8%). Of the 309 mutations related to autosomal-recessive disorders, 240 (77.7%) were variants found in gnomAD. Of these variants, 202 (84.2%) were documented among one or more Ashkenazi individuals. At this point in the INGD, there are 168 Ashkenazi assumed founder mutations in 128 different genes corresponding to 111 autosomal-recessive disorders.
Conclusion: Integration of information on mutations among Ashkenazi Jews extracted from the INGD with their population frequency recorded in gnomAD is important for effective straightforward molecular diagnosis as well as for targeted carrier screening either for reproductive decision-making or for implementation of disease-modifying behavior.
Keywords: Ashkenazi Jews; founder mutations; gnomAD; screening.