ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.257C>G (p.Pro86Arg) (rs2229222)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000399666 SCV000407256 uncertain significance Glycogen storage disease, type II 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000595797 SCV000702184 benign not specified 2016-10-05 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000595797 SCV000917389 likely benign not specified 2018-02-23 criteria provided, single submitter clinical testing Variant summary: GAA c.257C>G (p.Pro86Arg) involves the alteration of a conserved nucleotide that results in a non-conservative amino acid change located in the P-type trefoil domain (IPR000519) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1.78 fold of the estimated maximal expected allele frequency for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) phenotype (0.0042), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.257C>G in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000399666 SCV001013875 likely benign Glycogen storage disease, type II 2019-12-31 criteria provided, single submitter clinical testing

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