NM_000152.5(GAA):c.2702dup (p.Gln902fs) AND Glycogen storage disease, type II

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 19, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002870711.3

Allele description [Variation Report for NM_000152.5(GAA):c.2702dup (p.Gln902fs)]

NM_000152.5(GAA):c.2702dup (p.Gln902fs)

Gene:

GAA:alpha glucosidase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_000152.5(GAA):c.2702dup (p.Gln902fs)

HGVS:

NC_000017.11:g.80118708dup
NG_009822.1:g.22153dup
NM_000152.5:c.2702dupMANE SELECT
NM_001079803.3:c.2702dup
NM_001079804.3:c.2702dup
NM_001406741.1:c.2702dup
NM_001406742.1:c.2702dup
NP_000143.2:p.Gln902Alafs
NP_000143.2:p.Gln902fs
NP_001073271.1:p.Gln902fs
NP_001073272.1:p.Gln902fs
NP_001393670.1:p.Gln902Alafs
NP_001393671.1:p.Gln902Alafs
LRG_673t1:c.2702dup
LRG_673:g.22153dup
LRG_673p1:p.Gln902Alafs
NC_000017.10:g.78092506_78092507insT
NC_000017.10:g.78092507dup
NM_000152.3:c.2702dup

Protein change:

Q902fs

Molecular consequence:

NM_000152.5:c.2702dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001079803.3:c.2702dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001079804.3:c.2702dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406741.1:c.2702dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001406742.1:c.2702dup - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003221367	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 19, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22252923, 29122469, 31606152, 33741225, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003221367

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 19, 2022)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Predicting cross-reactive immunological material (CRIM) status in Pompe disease using GAA mutations: lessons learned from 10 years of clinical laboratory testing experience.

Bali DS, Goldstein JL, Banugaria S, Dai J, Mackey J, Rehder C, Kishnani PS.

Am J Med Genet C Semin Med Genet. 2012 Feb 15;160C(1):40-9. doi: 10.1002/ajmg.c.31319. Epub 2012 Jan 17.

PubMed [citation]

PMID:: 22252923
PMCID:: PMC3278076

Sensitivity of whole exome sequencing in detecting infantile- and late-onset Pompe disease.

Mori M, Haskell G, Kazi Z, Zhu X, DeArmey SM, Goldstein JL, Bali D, Rehder C, Cirulli ET, Kishnani PS.

Mol Genet Metab. 2017 Dec;122(4):189-197. doi: 10.1016/j.ymgme.2017.10.008. Epub 2017 Oct 17.

PubMed [citation]

PMID:: 29122469
PMCID:: PMC5907499

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003221367.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change results in a frameshift in the GAA gene (p.Gln902Alafs*116). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 51 amino acid(s) of the GAA protein and extend the protein by 64 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GAA-related conditions. This variant disrupts a region of the GAA protein in which other variant(s) (p.Tyr928Cys) have been determined to be pathogenic (PMID: 22252923, 29122469, 31606152, 33741225). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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