ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.258C>A (p.Pro86=)

gnomAD frequency: 0.00170  dbSNP: rs146615896
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel RCV001001756 SCV004227905 likely benign Glycogen storage disease, type II 2023-12-05 reviewed by expert panel curation The NM_000152.5: c.258C>A (p.Pro86=) variant in GAA is a synonymous variant with a highest population minor allele frequency in gnomAD v4.0.0 of 0.00509 (382/75054 alleles) in the African/African American population, which is higher than the ClinGen Lysosomal Diseases (LD) VCEP’s threshold for BS1 (>0.005), meeting this criterion (BS1). The variant is not predicted to impact splicing; the nucleotide is not conserved (BP4, BP7). There is a ClinVar entry for this variant (Variation ID: 282138). In summary, this variant meets the criteria to be classified as likely benign for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases VCEP (Specifications Version 2.0): BS1, BP4, BP7. (Classification approved by the ClinGen Lysosomal Diseases VCEP on December 5, 2023).
Eurofins Ntd Llc (ga) RCV000338982 SCV000333379 benign not specified 2015-07-21 criteria provided, single submitter clinical testing
GeneDx RCV000590222 SCV000523296 likely benign not provided 2020-09-08 criteria provided, single submitter clinical testing
Invitae RCV001001756 SCV000626585 benign Glycogen storage disease, type II 2024-01-31 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590222 SCV000695657 likely benign not provided 2017-02-03 criteria provided, single submitter clinical testing Variant summary: The GAA c.258C>A (p.Pro86Pro) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect binding of an ESE site. These predictions have yet to be confirmed by functional studies. This variant was found in 69/114570 control chromosomes from ExAC, predominantly observed in the African subpopulation at a frequency of 0.006696 (64/9558). This frequency is about 1.6 times the estimated maximal expected allele frequency of a pathogenic GAA variant (0.0042205), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. No homozygotes have been reported in ExAC. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. A clinical diagnostic laboratory in ClinVar has classified this variant as benign. Taken together, this variant is classified as Likely Benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001001756 SCV001159368 benign Glycogen storage disease, type II 2022-03-07 criteria provided, single submitter clinical testing

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