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]

Variant: NM_000152.5(GAA):c.1961C>A (p.Ser654Ter)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA16043014

372968 (ClinVar)

Gene: GAA

Condition: glycogen storage disease II

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 1c44650b-cb84-4ebf-98b5-8d7696e6a2f6

Approved on: 2020-05-04

Published on: 2020-05-27

HGVS expressions

NM_000152.5:c.1961C>A

NM_000152.5(GAA):c.1961C>A (p.Ser654Ter)

NC_000017.11:g.80112948C>A

CM000679.2:g.80112948C>A

NC_000017.10:g.78086747C>A

CM000679.1:g.78086747C>A

NC_000017.9:g.75701342C>A

NG_009822.1:g.16393C>A

ENST00000570803.6:c.1961C>A

ENST00000572080.2:c.*99C>A

ENST00000577106.6:c.1961C>A

ENST00000302262.8:c.1961C>A

ENST00000302262.7:c.1961C>A

ENST00000390015.7:c.1961C>A

ENST00000570716.1:n.401C>A

ENST00000572080.1:c.380C>A

ENST00000572803.1:n.575C>A

NM_000152.3:c.1961C>A

NM_001079803.1:c.1961C>A

NM_001079804.1:c.1961C>A

NM_000152.4:c.1961C>A

NM_001079803.2:c.1961C>A

NM_001079804.2:c.1961C>A

NM_001079803.3:c.1961C>A

NM_001079804.3:c.1961C>A

Likely Pathogenic

PVS1 PM2

Evidence Links 0

Expert Panel

Lysosomal Diseases VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Lysosomal Diseases VCEP

This variant, c.1961C>A (p.Ser654Ter), is a nonsense variant that is predicted to result in nonsense mediated decay and lack of gene product, meeting PVS1. The variant is absent in gnomAD v2.1.1, meeting PM2. To our knowledge, this variant has not been reported in the literature in any individual with Pompe disease. However, there is a ClinVar entry for this variant (Variation ID 372968) with one submitter classifying the variant as likely 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.

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 v2.1.1.

Curation History

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