Variant: NM_000152.5(GAA):c.2400C>T (p.Ser800=)

CA180077

167115 (ClinVar)

Gene: GAA

Condition: glycogen storage disease II

Inheritance Mode: Autosomal recessive inheritance

UUID: f1b0a8d8-3cc5-4dc5-9a2a-21e4715f92e1

Approved on: 2024-08-06

Published on: 2024-09-03

HGVS expressions

NM_000152.5:c.2400C>T
NM_000152.5(GAA):c.2400C>T (p.Ser800=)
NC_000017.11:g.80117668C>T
CM000679.2:g.80117668C>T
NC_000017.10:g.78091467C>T
CM000679.1:g.78091467C>T
NC_000017.9:g.75706062C>T
NG_009822.1:g.21113C>T
ENST00000570803.6:c.2400C>T
ENST00000572080.2:c.*538C>T
ENST00000577106.6:c.2400C>T
ENST00000302262.8:c.2400C>T
ENST00000302262.7:c.2400C>T
ENST00000390015.7:c.2400C>T
ENST00000573556.1:n.353C>T
NM_000152.3:c.2400C>T
NM_001079803.1:c.2400C>T
NM_001079804.1:c.2400C>T
NM_000152.4:c.2400C>T
NM_001079803.2:c.2400C>T
NM_001079804.2:c.2400C>T
NM_001079803.3:c.2400C>T
NM_001079804.3:c.2400C>T

Benign

• Met criteria codes: BA1

• Not Met criteria codes: PM2

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

Evidence submitted by expert panel

Lysosomal Diseases VCEP

The NM_000152.5:c.2400C>T variant in GAA is a synonymous (silent) variant (p.Ser800=) that is not predicted to impact splicing. The highest population minor allele frequency in gnomAD v2.1.1. is 0.02504 (617/24640 alleles; 9 homozygotes) in the African/African American population, which is higher than the ClinGen Lysosomal Diseases VCEP’s threshold for BA1 (>0.01), and therefore meets this criterion (BA1). There is a ClinVar entry for this variant (Variation ID: 167115. In summary, this variant meets the criteria to be classified as Benign for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen Lysosomal Diseases Variant Curation Expert Panel (specifications Version 2.0): BA1. (Classification approved by the ClinGen Lysosomal Diseases Variant Curation Expert Panel on August 6, 2024).

Met criteria codes

• BA1: The highest population minor allele frequency in gnomAD v2.1.1. is 0.02504 (617/24640 alleles; 9 homozygotes) in the African/African American population, which is higher than the ClinGen Lysosomal Diseases VCEP’s threshold for BA1 (>0.01), and therefore meets this criterion (BA1).

Not Met criteria codes

• PM2: No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline