Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000152.5(GAA):c.1153del (p.Arg385fs)

CA658798978

501294 (ClinVar)

Gene: GAA

Condition: glycogen storage disease II

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: ee432de0-5d88-4fc1-be4c-e9cc41b8a483

HGVS expressions

NM_000152.5:c.1153del

NM_000152.5(GAA):c.1153del (p.Arg385fs)

NM_000152.3:c.1153del

NM_001079803.1:c.1153del

NM_001079804.1:c.1153del

NM_000152.4:c.1153del

NM_001079803.2:c.1153del

NM_001079804.2:c.1153del

NM_001079803.3:c.1153del

NM_001079804.3:c.1153del

ENST00000302262.7:c.1153del

ENST00000390015.7:c.1153del

NC_000017.11:g.80108566del

CM000679.2:g.80108566del

NC_000017.10:g.78082365del

CM000679.1:g.78082365del

NC_000017.9:g.75696960del

NG_009822.1:g.12011del

Pathogenic

PP4 PM3_Supporting PM2 PVS1

Evidence Links 1

Expert Panel

Lysosomal Diseases VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Lysosomal Diseases VCEP

This variant, c.1153del (p.Arg385AlafsTer7), is a frameshift variant that is predicted to result in a premature termination codon, nonsense mediated decay, and lack of gene product, meeting PVS1. This variant is not in gnomAD v2.1.1, meeting PM2. One patient has been reported who meets the ClinGen LSD VCEP’s specifications for PP4 and who is compound heterozygous for the variant and c.-32-13T>G, phase unknown (28554557). PM3_Supporting is met. There is a ClinVar entry for this variant (Variation ID: 501294, 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, PM2, PM3_Supporting, PP4.

PP4

One patient has been reported with residual GAA activity in the affected range in a dried blood spot assay, meeting PP4.

PM3_Supporting

One patient has been reported who meets the ClinGen LSD VCEP’s specifications for PP4 and who is compound heterozygous for the variant and c.-32-13T>G, phase unknown (28554557). PM3_Supporting is met (0.5 points)

PubMed:28554557

PM2

This variant is not in gnomAD v2.1.1.

PVS1

This is a frameshift variant which is predicted to result in a premature termination codon, nonsense mediated decay, and lack of gene product. Therefore, PVS1 can be applied.

Approved on: 2020-08-31

Published on: 2020-11-12

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