NM_000152.5(GAA):c.2189+1G>T AND Glycogen storage disease, type II

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Jul 20, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000674456.3

Allele description [Variation Report for NM_000152.5(GAA):c.2189+1G>T]

NM_000152.5(GAA):c.2189+1G>T

Gene:

GAA:alpha glucosidase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_000152.5(GAA):c.2189+1G>T

HGVS:

NC_000017.11:g.80113367G>T
NG_009822.1:g.16812G>T
NG_137936.1:g.652G>T
NM_000152.5:c.2189+1G>TMANE SELECT
NM_001079803.3:c.2189+1G>T
NM_001079804.3:c.2189+1G>T
NM_001406741.1:c.2189+1G>T
NM_001406742.1:c.2189+1G>T
LRG_673t1:c.2189+1G>T
LRG_673:g.16812G>T
NC_000017.10:g.78087166G>T
NM_000152.3:c.2189+1G>T

Links:

dbSNP: rs1209887739

NCBI 1000 Genomes Browser:

rs1209887739

Molecular consequence:

NM_000152.5:c.2189+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001079803.3:c.2189+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001079804.3:c.2189+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406741.1:c.2189+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001406742.1:c.2189+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Observations:

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
SCV000799795	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (May 7, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001976529	Breda Genetics srl	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 30, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25783438, 25741868
SCV002808761	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 20, 2021)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000799795

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(May 7, 2018)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV001976529

Breda Genetics srl

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 30, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002808761

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 20, 2021)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

LOPED study: looking for an early diagnosis in a late-onset Pompe disease high-risk population.

Musumeci O, la Marca G, Spada M, Mondello S, Danesino C, Comi GP, Pegoraro E, Antonini G, Marrosu G, Liguori R, Morandi L, Moggio M, Massa R, Ravaglia S, Di Muzio A, Filosto M, Tonin P, Di Iorio G, Servidei S, Siciliano G, Angelini C, Mongini T, et al.

J Neurol Neurosurg Psychiatry. 2016 Jan;87(1):5-11. doi: 10.1136/jnnp-2014-310164. Epub 2015 Mar 17.

PubMed [citation]

PMID:: 25783438

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Counsyl, SCV000799795.1

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

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

From Breda Genetics srl, SCV001976529.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		1	not provided	not provided	clinical testing	PubMed (2)

Description

The variant c.2189+1G>T in the GAA gene is reported as likely pathogenic for glycogen storage disease type 2 (Pompe disease) in ClinVar (Variation ID: 558223). The variant was identified by Musumeci et al., 2015 (PMID: 25783438) in a female patient with late-onset Pompe disease (age of onset at 28 years), who was compound heterozygote with the common mutation c.-32-13T>G. The study was conducted in a cohort of patients with late-onset disease (after five years of age). The variant affects the donor splice site of intron 15 and is therefore highly likely to impact the splicing process by causing the retention of the following intron and the formation of an aberrant mRNA, which is unlikely to be exported and translated into protein. There is no information on frequency in gnomAD database.

#	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		1	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002808761.1

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

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

Last Updated: Mar 16, 2024

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