ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.1802C>A (p.Ser601Ter)

dbSNP: rs374470794
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel RCV001205738 SCV001443285 pathogenic Glycogen storage disease, type II 2020-06-03 reviewed by expert panel curation This variant, c.1802C>A (p.Ser601Ter), which results in a premature termination codon, is expected to result in nonsense mediated decay and absence of gene product, meeting PVS1. This is supported by the finding that a patient with this variant has no GAA cross-reactive immunological material in protein isolated from skin fibroblast cultures i.e. CRIM-negative (PMID 21687968). The variant is absent in gnomAD v2.1.1, meeting PM2. This variant was found in compound heterozygosity with c.525del in one patient with Pompe disease meeting the specifications for PP4. The phase is unknown (PMID 26497565). This data meets PM3_Supporting. A patient with the same genotype has been reported (PMID 21687968) and might be the same patient but this could not be verified. There is a ClinVar entry for this variant (Variation ID: 593486, 1 star review status) with one submitter classifying the variant as pathogenic. In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: PVS1, PM3_Suporting, PM2, PP4.
Eurofins Ntd Llc (ga) RCV000728538 SCV000856128 pathogenic not provided 2017-07-31 criteria provided, single submitter clinical testing
Invitae RCV001205738 SCV001377009 pathogenic Glycogen storage disease, type II 2023-09-08 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 593486). This premature translational stop signal has been observed in individuals with GAA-related conditions (PMID: 21687968, 29422078). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser601*) in the GAA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GAA are known to be pathogenic (PMID: 18425781, 22252923).
CeGaT Center for Human Genetics Tuebingen RCV000728538 SCV001502246 pathogenic not provided 2020-08-01 criteria provided, single submitter clinical testing

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