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NM_000152.5(GAA):c.2655_2656del (p.Val886fs) AND Glycogen storage disease, type II

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 1, 2021
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001789710.3

Allele description [Variation Report for NM_000152.5(GAA):c.2655_2656del (p.Val886fs)]

NM_000152.5(GAA):c.2655_2656del (p.Val886fs)

Gene:
GAA:alpha glucosidase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
17q25.3
Genomic location:
Preferred name:
NM_000152.5(GAA):c.2655_2656del (p.Val886fs)
Other names:
NM_000152.5(GAA):c.2655_2656del; p.Val886fs
HGVS:
  • NC_000017.11:g.80118661_80118662del
  • NG_009822.1:g.22106_22107del
  • NM_000152.5:c.2655_2656delMANE SELECT
  • NM_001079803.3:c.2655_2656del
  • NM_001079804.3:c.2655_2656del
  • NP_000143.2:p.Val886fs
  • NP_001073271.1:p.Val886fs
  • NP_001073272.1:p.Val886fs
  • LRG_673:g.22106_22107del
  • NC_000017.10:g.78092460_78092461del
Protein change:
V886fs
Links:
dbSNP: rs1555603219
NCBI 1000 Genomes Browser:
rs1555603219
Molecular consequence:
  • NM_000152.5:c.2655_2656del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001079803.3:c.2655_2656del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001079804.3:c.2655_2656del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Glycogen storage disease, type II (GSD2)
Synonyms:
ACID ALPHA-GLUCOSIDASE DEFICIENCY; GLYCOGENOSIS, GENERALIZED, CARDIAC FORM; GSD II; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009290; MedGen: C0017921; Orphanet: 365; OMIM: 232300

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002032121ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel
reviewed by expert panel

(clingen_lsd_acmg_specifications_v2-1)		Pathogenic
(Sep 1, 2021) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel, SCV002032121.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_000152.5:c.2655_2656del (p.Val886GlufsTer2) variant in GAA is a frameshift variant predicted to cause a premature stop codon and to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). Two siblings with this variant and late-onset Pompe disease have been reported with GAA activity in dried blood spots below the normal range, and both are on enzyme replacement therapy (PMID 31392188, personal communication)(PP4_Moderate). These individuals are compound heterozygous for the variant and a pathogenic variant in GAA, c.-32-13T>G, phase unknown (PM3_Supporting). The variant is absent in gnomAD v2.1.1 (PM2_Supporting). There is a ClinVar entry for this variant (Variation ID: 597005; 1 star review status) with one submitter classifying the variant as pathogenic. In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria met, based on the specifications of the ClinGen LSD VCEP (Specifications Version 2.0): PVS1, PP4_Moderate, PM2_Supporting, PM3_Supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 1, 2023