ClinVar

Description

Variant summary: LRRK2 c.4894G>C (p.Glu1632Gln) results in a conservative amino acid change located in the C-terminal of Roc (COR) domain (IPR032171) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 249712 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4894G>C has been reported in the literature in individuals affected with dementia with Lewy bodies or chronic obstructive pulmonary disease (Rubio_2012, Keogh_2018). These reports do not provide unequivocal conclusions about association of the variant with Parkinson Disease 8, Autosomal Dominant. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 22415848, 30363439, 29332010). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.