ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2652G>A (p.Thr884=) (rs143642048)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000726336 SCV000343860 uncertain significance not provided 2018-04-23 criteria provided, single submitter clinical testing
Invitae RCV001085559 SCV000626589 likely benign Glycogen storage disease, type II 2020-11-26 criteria provided, single submitter clinical testing
GeneDx RCV000726336 SCV000724068 likely benign not provided 2021-05-05 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001085559 SCV001285669 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.
Nilou-Genome Lab RCV001085559 SCV001810199 uncertain significance Glycogen storage disease, type II 2021-07-22 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group, Broad Institute RCV001085559 SCV001422614 likely benign Glycogen storage disease, type II 2020-01-22 no assertion criteria provided curation The c.2652G>A (p.Thr884=) variant in GAA has not been previously reported in individuals with Glycogen Storage Disease II but has been reported as a VUS by EGL Genetic Diagnostics and a likely benign variant by GeneDx and Invitae in ClinVar (Variation ID: 289488). This variant has been identified in 0.135% (32/23756) of European (Finnish) chromosomes and 0.055% (71/128992) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs143642048). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. However, novel synonymous variants supported by computational evidence without raised suspicion for an impact are likely benign (Richards 2015). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely benign. ACMG/AMP Criteria applied: BP4, BP7 (Richards 2015).

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