NM_000158.4(GBE1):c.691+2T>C AND Glycogen storage disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 16, 2020
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:: RCV001449661.12

Allele description [Variation Report for NM_000158.4(GBE1):c.691+2T>C]

NM_000158.4(GBE1):c.691+2T>C

Gene:

GBE1:1,4-alpha-glucan branching enzyme 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p12.2

Genomic location:

Preferred name:

NM_000158.4(GBE1):c.691+2T>C

HGVS:

NC_000003.12:g.81648854A>G
NG_011810.1:g.117947T>C
NG_011810.2:g.117791T>C
NM_000158.4:c.691+2T>CMANE SELECT
NC_000003.11:g.81698005A>G
NM_000158.3:c.691+2T>C

Links:

dbSNP: rs192044702

NCBI 1000 Genomes Browser:

rs192044702

Molecular consequence:

NM_000158.4:c.691+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Observations:

Condition(s)

Name:: Glycogen storage disease
Synonyms:: glycogen storage disorder; Disorder of glycogen metabolism
Identifiers:: MONDO: MONDO:0002412; MedGen: C0017919; OMIM: PS232200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000245614	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Pathogenic (Jun 16, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19813197, 23218673, 30569318, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000245614

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Pathogenic
(Jun 16, 2020)

germline

clinical testing

PubMed (4)
[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	2	2	not provided	not provided	not provided	clinical testing

Citations

PubMed

Non-lethal neonatal neuromuscular variant of glycogenosis type IV with novel GBE1 mutations.

Fernandez C, Halbert C, De Paula AM, Lacroze V, Froissart R, Figarella-Branger D, Chabrol B, Pellissier JF.

Muscle Nerve. 2010 Feb;41(2):269-71. doi: 10.1002/mus.21499.

PubMed [citation]

PMID:: 19813197

Whole exome sequencing in foetal akinesia expands the genotype-phenotype spectrum of GBE1 glycogen storage disease mutations.

Ravenscroft G, Thompson EM, Todd EJ, Yau KS, Kresoje N, Sivadorai P, Friend K, Riley K, Manton ND, Blumbergs P, Fietz M, Duff RM, Davis MR, Allcock RJ, Laing NG.

Neuromuscul Disord. 2013 Feb;23(2):165-9. doi: 10.1016/j.nmd.2012.11.005. Epub 2012 Dec 3.

PubMed [citation]

PMID:: 23218673

See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000245614.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (4)

Description

The c.691+2T>C variant in GBE1 has been reported in at least 3 compound heterozygous individuals with glycogen storage disease IV and segregated with disease in at least 2 affected relatives from 1 family (Fernandez 2010 PMID:19813197, Ravenscroft 2013 PMID:23218673, Schene 2018 PMID:30569318). It has also been reported in ClinVar (Variation ID 208584) and has been identified in 0.14% (160/110918) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. Loss of function of the GBE1 gene is an established disease mechanism in autosomal recessive glycogen storage disease IV. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive glycogen storage disease IV. ACMG/AMP Criteria applied: PVS1, PM3_Strong, PP1_Moderate.

#	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		2	not provided	2	not provided

Last Updated: May 1, 2024

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Relating variation to medicine