ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.875A>G (p.Tyr292Cys) (rs1057516600)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410689 SCV000485930 likely pathogenic Glycogen storage disease, type II 2016-03-03 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000730212 SCV000857931 pathogenic not provided 2017-11-22 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000410689 SCV000919380 pathogenic Glycogen storage disease, type II 2018-04-16 criteria provided, single submitter clinical testing Variant summary: GAA c.875A>G (p.Tyr292Cys) results in a non-conservative amino acid change located in the Glycoside hydrolase family 31, N-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was observed with an allele frequency of 8.3e-06 in 241494 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) (8.3e-06 vs 0.0042), allowing no conclusion about variant significance. The variant, c.875A>G, has been reported in the literature in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease)(Gort_2007, Gutierrez-Rivas_2015, Hermans_2004, Park_2013). 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. The most pronounced variant effect results in 10%-<30% of normal activity. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cite the variant as "likely pathogenic." Based on the evidence outlined above, the variant was classified as pathogenic.

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