The pathogenicity prediction of a QDPR gene missensevariant, c.۳۷۴A>T (p.His۱۲۵Leu), using in silico tools

Defects in the quinoid dihydropteridine reductase (QDPR) gene may results in dihydropteridine reductase (DHPR)deficiency [۱]. Therefore, it is necessary to investigate the deleterious effects of new variants. The Iranome project(http://www.iranome.ir/) has recently been implemented in Iran and has led to the identification of several genomicvariants in the Iranian population [۲]. In this study, the pathogenicity prediction of a missense variant, QDPR:c.۳۷۴A>T (p.His۱۲۵Leu), which has recently been reported in the Iranome project is presented.Ten in silico predictive tools including PANTHER PSEP (http://pantherdb.org/), PhD-SNPg(https://snps.biofold.org/phd-snpg/#), PROVEAN and SIFT (both available at: http://provean.jcvi.org/index.php),Mutation Taster (http://www.mutationtaster.org/), SNPs & GO (https://snps.biofold.org/snps-and-go/), FATHMMXF(http://fathmm.biocompute.org.uk/fathmm-xf/), I-Mutant Disease (http://gpcr.biocomp.unibo.it/cgi/predictors/IMutant۳.۰/I-Mutant۳.۰.cgi), PolyPhen-۲ (http://genetics.bwh.harvard.edu/pph۲/), CADD(https://cadd.gs.washington.edu/) were used in this study.The results of our analysis were as follows: PANTHER PSEP (probably damaging), PhD-SNPg (pathogenic),PROVEAN (deleterious), Mutation Taster (disease causing), SNPs & GO (Neutral), FATHMM-XF (pathogenic), IMutantDisease (disease), PolyPhen-۲ (Benign), CADD (score: ۲۲.۷), SIFT (Tolerated). In conclusion, with athreshold of deleterious effects in seven or more in silico predictive tools, QDPR: c.۳۷۴A>T (p.His۱۲۵Leu) variantcould be accepted as a pathogenic variant. However, for its final classification, it is necessary to consider the othercriteria provided by American College of Medical Genetics and Genomics (ACMG-AMP) guidelines [۳].

کلیدواژه ها:

DHPR deficiency ، QDPR gene ، in silico analysis.