ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.2136_2137del (p.Phe713fs)

dbSNP: rs1555601780
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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 RCV000672761 SCV002032112 pathogenic Glycogen storage disease, type II 2021-08-19 reviewed by expert panel curation The NM_000152.5:c.2136_2137del (p.Phe713ProfsTer23) variant in GAA is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 15/20, predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). A patient with this variant was reported to have deficient GAA activity and to be on enzyme replacement therapy for Pompe disease (PMID: 25614309, 27896092)(PP4). This patient is compound heterozygous, phase unknown, for the variant and a pathogenic variant in GAA, c.-32-13T>G ( PMID: 25614309, 27896092)(PM3_Supporting). There is a ClinVar entry for this variant (Variation ID: 556718; 1 star review status) with one submitter classifying the variant as likely pathogenic. In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria met, based on the specifications of the ClinGen Lysosomal Storage Disorders VCEP (Specification Version 2.0): PVS1, PM2_Supporting, PM3_Supporting, PP4. (Classification approved on August 17th, 2021)
Counsyl RCV000672761 SCV000797899 likely pathogenic Glycogen storage disease, type II 2018-02-14 criteria provided, single submitter clinical testing
Invitae RCV000672761 SCV002134523 pathogenic Glycogen storage disease, type II 2021-11-27 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 556718). This variant is also known as c.2136-7delGT. This premature translational stop signal has been observed in individual(s) with Pompe disease (PMID: 25614309). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe713Profs*23) 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).
Baylor Genetics RCV000672761 SCV004197841 pathogenic Glycogen storage disease, type II 2023-04-24 criteria provided, single submitter clinical testing

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