ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.369+1G>A

dbSNP: rs797044669
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000175538 SCV000227041 pathogenic not provided 2015-04-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001293581 SCV001482193 pathogenic Fabry disease 2021-02-23 criteria provided, single submitter clinical testing Variant summary: GLA c.369+1G>A (also known as IVS2+1G>A) 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: Three predict the variant abolishes a 5' splicing donor site. The variant was absent in 182894 control chromosomes. c.369+1G>A has been reported in the literature in individuals affected with Fabry Disease (Ashton-Prolla_2000, Kobayashi_2019, Kramer_2018, etc). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function and reports the variant to have significantly dimished alpha-Gal activity, and showed chaperone incubation did not result in increased a-Gal activity in immortalised IVS2+1G>A cells (Lenders_2019). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab RCV001293581 SCV002054441 pathogenic Fabry disease 2021-07-15 criteria provided, single submitter clinical testing

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