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.1332T>C (p.Pro444=)

CA8815288

286018 (ClinVar)

Gene: GAA

Condition: glycogen storage disease II

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 6677c5dc-80b2-4ac1-b197-6c8a76d3a6a9

HGVS expressions

NM_000152.5:c.1332T>C

NM_000152.5(GAA):c.1332T>C (p.Pro444=)

NC_000017.11:g.80109950T>C

CM000679.2:g.80109950T>C

NC_000017.10:g.78083749T>C

CM000679.1:g.78083749T>C

NC_000017.9:g.75698344T>C

NG_009822.1:g.13395T>C

ENST00000302262.8:c.1332T>C

ENST00000302262.7:c.1332T>C

ENST00000390015.7:c.1332T>C

NM_000152.3:c.1332T>C

NM_001079803.1:c.1332T>C

NM_001079804.1:c.1332T>C

NM_000152.4:c.1332T>C

NM_001079803.2:c.1332T>C

NM_001079804.2:c.1332T>C

NM_001079803.3:c.1332T>C

NM_001079804.3:c.1332T>C

Likely Benign

BP7 BP4 BS1

Evidence Links 0

Expert Panel

Lysosomal Diseases VCEP

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.1332T>C (p.Pro444=) variant in GAA is a synonymous (silent) variant that is not predicted to impact splicing; the nucleotide is not highly conserved (PhyloP 100 way score is -2.4 (BP4, BP7). There is a ClinVar entry for this variant (Variation ID: 286018). In summary, this variant meets the criteria to be classified as likely benign for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases VCEP (Specifications Version 2.0): BS1, BP4, BP7. (Classification approved by the ClinGen Lysosomal Diseases VCEP, March 13, 2023).

BP7

The NM_000152.5:c.1332T>C (p.Pro444=) variant in GAA is a synonymous (silent) variant that is not predicted to impact splicing; the nucleotide is not highy conserved (PhyloP 100 way score is -2.4 (BP7).

BP4

The computational splicing predictor SpliceAI suggests that the variant has no impact on splicing (BP4).

BS1

The highest population minor allele frequency in gnomAD v2.1.1 is 0.00859 (171/19912 alleles; including one homozygote) in the East Asian population, which is higher than the ClinGen Lysosomal Diseases VCEP threshold (>0.005) for BS1, and meets this criterion.

Approved on: 2023-03-13

Published on: 2023-03-13

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.