Variant: NM_000152.5(GAA):c.276C>A (p.Cys92Ter)

CA401360590

654482 (ClinVar)

Gene: GAA

Condition: glycogen storage disease II

Inheritance Mode: Autosomal recessive inheritance

UUID: c94287b0-819c-42f9-931c-1aabe0fe0d45

HGVS expressions

NM_000152.5:c.276C>A
NM_000152.5(GAA):c.276C>A (p.Cys92Ter)
NC_000017.11:g.80104862C>A
CM000679.2:g.80104862C>A
NC_000017.10:g.78078661C>A
CM000679.1:g.78078661C>A
NC_000017.9:g.75693256C>A
NG_009822.1:g.8307C>A
NM_000152.3:c.276C>A
NM_001079803.1:c.276C>A
NM_001079804.1:c.276C>A
NM_000152.4:c.276C>A
NM_001079803.2:c.276C>A
NM_001079804.2:c.276C>A
NM_001079803.3:c.276C>A
NM_001079804.3:c.276C>A
ENST00000302262.7:c.276C>A
ENST00000390015.7:c.276C>A
ENST00000570803.5:c.276C>A
ENST00000577106.5:c.276C>A

Likely Pathogenic

• Met criteria codes: PVS1 PM2

Expert Panel

Lysosomal Diseases VCEP

Criteria Specification Information

Evidence submitted by expert panel

Lysosomal Diseases VCEP

This variant, c.276C>A (p.Cys92Ter), is a nonsense variant that is predicted to result in nonsense-mediated decay and lack of gene product, meeting PVS1. This variant is absent in gnomAD v2.1.1, meeting PM2. To our knowledge, this variant has not been reported in individuals with Pompe disease in the literature and functional studies are unavailable. There is a ClinVar entry for this variant (Variation ID: 654482, 1 star review status) with one submitter classifying the variant as pathogenic. In summary, this variant meets the criteria to be classified as likely pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: PVS1, PM2.

Met criteria codes

• PVS1: This is a nonsense variant which is predicted to cause nonsense mediated decay resulting in no gene product. Therefore, PVS1 can be applied.
• PM2: This variant is absent in gnomAD.

Approved on: 2020-05-04

Published on: 2020-05-27