ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.169C>T (p.Gln57Ter) (rs1057516251)

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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, ClinGen RCV000412122 SCV001371706 pathogenic Glycogen storage disease, type II 2019-12-05 reviewed by expert panel curation This variant, c.169C>T (p.Gln57Ter), is a nonsense variant that is predicted to result in nonsense mediated decay and lack of gene product. Therefore, PVS1 can be applied. The variant is absent in gnomAD v2.1.1, meeting PM2. One individual meeting the ClinGen LSD VCEP's specifications for PP4 has been reported who is compound heterozygous for the variant and a missense variant in GAA, c.655G>A (p.Gly219Arg)(PMID 29124041). This in trans data will be used in the assessment of p.Gly219Arg and, therefore, was not included here in order to avoid circular logic. There is a ClinVar entry for this variant (Variation ID: 370124, two star review status) with one submitter classifying the variant and pathogenic and one as likely pathogenic. In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. ACMG/AMP criteria met, based on the specifications of the ClinGen LSD VCEP: PVS1, PM2, PP4.
Counsyl RCV000412122 SCV000485359 likely pathogenic Glycogen storage disease, type II 2015-11-24 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000412122 SCV000894160 pathogenic Glycogen storage disease, type II 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000412122 SCV001396302 pathogenic Glycogen storage disease, type II 2019-04-30 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln57*) in the GAA gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Pompe disease (PMID: 29124014). ClinVar contains an entry for this variant (Variation ID: 370124). Loss-of-function variants in GAA are known to be pathogenic (PMID: 18425781, 22252923). For these reasons, this variant has been classified as Pathogenic.

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