ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.546+18G>A

gnomAD frequency: 0.00474  dbSNP: rs190153982
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins NTD LLC (GA) RCV000398318 SCV000332713 benign not specified 2015-07-30 criteria provided, single submitter clinical testing
GeneDx RCV000398318 SCV000522170 likely benign not specified 2017-09-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001968 SCV001159770 benign Glycogen storage disease, type II 2020-10-20 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000398318 SCV001361269 benign not specified 2019-03-11 criteria provided, single submitter clinical testing Variant summary: GAA c.546+18G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0014 in 255508 control chromosomes, predominantly at a frequency of 0.015 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 4-folds higher than 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 African origin. To our knowledge, no occurrence of c.546+18G>A in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant twice as likely benign and once as benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV001001968 SCV001732782 benign Glycogen storage disease, type II 2021-12-18 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories,Mayo Clinic RCV000675215 SCV000800859 likely benign not provided 2017-04-17 no assertion criteria provided clinical testing

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