NM_000152.5(GAA):c.2704_2716dup (p.Val906fs) AND Glycogen storage disease, type II

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 26, 2021
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:: RCV000408809.5

Allele description [Variation Report for NM_000152.5(GAA):c.2704_2716dup (p.Val906fs)]

NM_000152.5(GAA):c.2704_2716dup (p.Val906fs)

Gene:

GAA:alpha glucosidase [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_000152.5(GAA):c.2704_2716dup (p.Val906fs)

HGVS:

NC_000017.11:g.80118710_80118722dup
NG_009822.1:g.22155_22167dup
NM_000152.5:c.2704_2716dupMANE SELECT
NM_001079803.3:c.2704_2716dup
NM_001079804.3:c.2704_2716dup
NP_000143.2:p.Val906fs
NP_001073271.1:p.Val906fs
NP_001073272.1:p.Val906fs
LRG_673t1:c.2704_2716dup
LRG_673:g.22155_22167dup
NC_000017.10:g.78092505_78092506insCTGCAGAAGGTGA
NC_000017.10:g.78092509_78092521dup
NM_000152.3:c.2704_2716dupCAGAAGGTGACTG

Protein change:

V906fs

Links:

dbSNP: rs1057516189

NCBI 1000 Genomes Browser:

rs1057516189

Molecular consequence:

NM_000152.5:c.2704_2716dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001079803.3:c.2704_2716dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001079804.3:c.2704_2716dup - 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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Mus musculus methyltransferase 4, N6-adenosine (Mettl4), transcript variant 3, m...
Mus musculus methyltransferase 4, N6-adenosine (Mettl4), transcript variant 3, mRNA
gi|2781670865|ref|NM_176917.6|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000484913	Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV003025857	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 26, 2021)	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

SCV000484913

Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare

no assertion criteria provided

Pathogenic

germline

clinical testing

SCV003025857

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 26, 2021)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
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 Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare, SCV000484913.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003025857.2

#	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.Val906Alafs*116). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 47 amino acid(s) of the GAA protein and extend the protein by 68 additional amino acid residues. This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 369944). This variant has not been reported in the literature in individuals affected with GAA-related conditions.

#	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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