ClinVar Miner

Submissions for variant NM_000157.4(GBA):c.762-1G>C (rs1237637353)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000781413 SCV000919420 pathogenic Gaucher disease 2018-12-24 criteria provided, single submitter clinical testing Variant summary: GBA c.762-1G>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a 3 acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing, leading to exon 7 skipping (Suwannarat_2007). The variant allele was found at a frequency of 7.3e-06 in 275322 control chromosomes (gnomAD). The variant, c.762-1G>C, has been reported in the literature in individuals affected with Gaucher Disease, in one homozygote and in another family in two compound heterozygotes siblings (Feng_2018, Suwannarat_2007). At least one publication reports experimental evidence evaluating an impact on protein function, with approximately 13% of normal GBA activity in peripheral leukocytes of a homozygote patient (Feng_2018). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Institute of Human Genetics,Klinikum rechts der Isar RCV000995774 SCV001150115 pathogenic Parkinson disease, late-onset 2019-06-07 criteria provided, single submitter clinical testing

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