Evidence Repository
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
  • No ClinVar Id was directly found from the curated document
  • ClinVar Id was derived from the Allele Registry.

Variant: NM_000152.5:c.1553_1555dup

CA913186005

932901 (ClinVar)

Gene: GAA
Condition: glycogen storage disease II
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 42aef045-9871-455c-9ebf-430f31cf07d4

HGVS expressions

NM_000152.5:c.1553_1555dup
NC_000017.11:g.80110942_80110944dup
CM000679.2:g.80110942_80110944dup
NC_000017.10:g.78084741_78084743dup
CM000679.1:g.78084741_78084743dup
NC_000017.9:g.75699336_75699338dup
NG_009822.1:g.14387_14389dup
ENST00000302262.8:c.1553_1555dup
ENST00000302262.7:c.1553_1555dup
ENST00000390015.7:c.1553_1555dup
NM_000152.3:c.1553_1555dup
NM_001079803.1:c.1553_1555dup
NM_001079804.1:c.1553_1555dup
NM_000152.4:c.1553_1555dup
NM_001079803.2:c.1553_1555dup
NM_001079804.2:c.1553_1555dup
NM_001079803.3:c.1553_1555dup
NM_001079804.3:c.1553_1555dup
NM_000152.5(GAA):c.1553_1555dup (p.Asp518_Met519insAsn)

Uncertain Significance

Met criteria codes 3
PP3 PM2_Supporting PM4_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Lysosomal Storage Disorders Variant Curation Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 2

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Lysosomal Diseases VCEP
The NM_000152.5:c.1553_1555dup variant in GAA is predicted to cause a change in the length of the protein (p.Asp518_Met519insAsn) due to an in-frame insertion of one amino acid in a non-repeat region (PM4_Supporting). The variant is absent in gnomAD v2.1.1 (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in individuals with Pompe disease, and results of experimental studies are not available. PROVEAN and Mutation Taster predict that this variant will impact the function of GAA (PP3). The is a ClinVar entry for this variant (Variation ID: 932901). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for Pompe disease. ACMG/AMP GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert Panel: PM2_Supporting, PM4_Supporting, PP3. (Classification approved by the ClinGen LD VCEP on May 29, 2023)
Met criteria codes
PP3
Computational evidence suggests that this variant impacts the function of GAA. The PROVEAN score is -9.75 (meeting the threshold of -2.5 for deleterious), and Mutation Taster predicts that this variant is "disease causing” (PP3). No impact on splicing is predicted by SpliceAI.
PM2_Supporting
This variant is absent in gnomAD v2.1.1 (PM2_Supporting).
PM4_Supporting
The NM_000152.5:c.1553_1555dup variant in GAA is predicted to cause a change in the length of the protein (p.Asp518_Met519insAsn) due to an in-frame insertion of one amino acid in a non-repeat region (PM4_Supporting).
Approved on: 2023-05-29
Published on: 2023-05-29
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