ClinVar

Description

Variant summary: The variant involves the duplication of exons 2-3 in the PRKN gene. It is assumed to be a tandem duplication in direct orientation (PMIDs: 25640679, 30054569). This Copy Number Variant (CNV) is predicted to result in an in-frame duplication within this gene. A presumed nomenclature of c.(7+1_8-1)_(412+1_413-1)dup has been designated for the purposes of this classification. Similar variant allele was found at a frequency of 4.6e-05 in 21692 control chromosomes (gnomAD, Structural Variants Dataset). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.(7+1_8-1)_(412+1_413-1)dup has been reported in the literature in individuals affected with Autosomal Recessive Parkinson Disease/Early-Onset Parkinsons Disease (examples: Periquet_2003, Lesage_2020, Hua_2022) and Autism (Yin_2016). However, only one of these individuals had an informative genotype (Hua_2022). Therefore, these publications do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 583436). Based on the evidence outlined above, the variant was classified as uncertain significance.