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A Compendium of manually annotated genetic variants for Alkaptonuria-AKUHub

S, A.; T.C, A. K.; S, S.; S, S.; N, S.; R, V.; Scaria, V.; Mehta, R. B.

2023-02-23 genetic and genomic medicine
10.1101/2023.02.21.23286262 medRxiv
Show abstract

1.Alkaptonuria or black urine disease is a rare autosomal recessive disorder caused by dysfunctional homogentisate 1,2-dioxygenase (HGD) gene (3q13.33) leading to accumulation of homogentisic acid in the body. This inborn error in metabolism of phenylalanine and tyrosine causes accumulation of homogentisic acid leading to ochronosis, pigmentation in the sclera, ear cartilage, mitral valve calcification and osteoarthropathy. Advances in sequencing technologies have helped us to map genetic variants associated with alkaptonuria in diverse populations and regions. Currently, no centralized resource of all the reported actionable variants with uniformity in annotation exists for the HGD gene. We have compiled HGD exonic variants from various data sources and systematically annotated their pathogenicity according to American College of Medical Genetics and the Association of Molecular Pathologists (ACMG/AMP) variant classification framework. A total of 1686 exonic variants were catalogued and manually curated, creating one of the most comprehensive Alkaptonuria variant databases (AKUHub) which is publicly available.

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