The gnomAD browser showed that the identified ELANE variant (NM_001972.4:c.170C>A) in the patient has never been described in the Asian population. However, this statement contradicts a reference cited in the manuscript (Park CH, Park S, Kim YJ, Kim SH, Kim HJ. Cyclic Neutropenia From a Novel Mutation Ala57Asp of ELANE: Phenotypic Variability in Neutropenia From Mutated Ala57 Residue. J Pediatr Hematol Oncol (2020) 42: e231-34. doi:10.1097/MPH.0000000000001353), which describes a Korean patient with the same ELANE variant.
Hello xinying_chen, thank you for reaching out with your concerns.
This is actually the behavior we would expect to see in gnomAD. As noted on our about page , gnomAD is depleted of individuals with severe pediatric disease-causing variation. It looks like your shared paper fits this case, however, with a disease onset at 7 years of age.
Again from that ‘about’ page, “the gnomAD resource should serve as useful reference sets of allele frequencies for severe pediatric disease studies” , for comparing these cases against. It’s the expected behavior that a ‘novel missense mutation’ where ‘previously reported missense mutations (Ala57Ser/Thr/Val) were observed in severe congenital neutropenia cases’ would not be observed in this dataset.
Thank you for your question, and don’t hesitate to reach out with further questions in the future! Let me know if there are any further comments or questions or concerns.
- Daniel Marten, gnomAD Production Team