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Updated: Jul 14, 2025

Determining the Likelihood of Variant Pathogenicity Using Amino Acid-level Signal-to-Noise Analysis of Genetic Variation
Published on: January 16, 2019
Impact of ACE2 gene variations on COVID-19 pathogenicity in Pakistani patients
Yar Muhammad Waryah1,2, Feriha Fatima Khidri3,4, Roohi Nigar5
1Scientific Ophthalmic and Research Laboratory, Sindh Institute of Ophthalmology and Visual Sciences, Hyderabad 71500, Pakistan.
Background:
COVID-19, caused by the SARS-CoV-2 virus, swiftly disseminated and was declared a pandemic. Variations in the ACE2 gene can impact the virus's ability to bind to ACE2 receptor, potentially influencing an individual's susceptibility and its association with COVID-19 severity across various populations.
Methods:
In total, 200 individuals were sequenced for the ACE2 gene and potential impact of the found variants on the ACE2 protein was assessed using in-silico tools.
Results:
Eight variations in the ACE2 gene were identified in 27 COVID-19 patients, of which four were missense and four were intronic variants. Three variants had a MAF of < 0.01 (c.251C > T, p.Pro86Leu; 15C > G, p.S5S; and c. 91 A > G, p.Lys31Glu). A missense variant, p.Pro86Leu, C > T, TT genotype, was found in 9 out of 200 individuals with an allele frequency of 0.045 and showed a significant association with COVID-19 (P = 0.003). The heterozygous allele of 15C > G, p.S5S, was found with a frequency of 0.02 (8/400) in eight patients, and its CG genotype showed a significant association with COVID-19 (P = 0.0068). The remaining identified variants were not associated with COVID-19 susceptibility.
Conclusion:
The ACE2 gene sequence in Pakistani individuals exhibited a low frequency of identified variants in COVID-19 patients. Overall, only two variants were associated with susceptibility to the disease, possibly contributing to Pakistan's lower COVID-19 mortality and infection rates. However, individuals carrying the mutant variant experienced more severe symptoms.
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