NM_000152.5(GAA):c.118C>T (p.Arg40Ter) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 20, 2023
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:: RCV000489843.7

Allele description [Variation Report for NM_000152.5(GAA):c.118C>T (p.Arg40Ter)]

NM_000152.5(GAA):c.118C>T (p.Arg40Ter)

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.118C>T (p.Arg40Ter)

HGVS:

NC_000017.11:g.80104704C>T
NG_009822.1:g.8149C>T
NM_000152.3(GAA):c.118C>T
NM_000152.5:c.118C>TMANE SELECT
NM_001079803.3:c.118C>T
NM_001079804.3:c.118C>T
NP_000143.2:p.Arg40Ter
NP_001073271.1:p.Arg40Ter
NP_001073272.1:p.Arg40Ter
LRG_673t1:c.118C>T
LRG_673:g.8149C>T
NC_000017.10:g.78078503C>T
NM_000152.3(GAA):c.118C>T
NM_000152.3:c.118C>T
NM_000152.5:c.118C>T
p.Arg40Ter

Protein change:

R40*

Links:

dbSNP: rs767409395

NCBI 1000 Genomes Browser:

rs767409395

Molecular consequence:

NM_000152.5:c.118C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001079803.3:c.118C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001079804.3:c.118C>T - nonsense - [Sequence Ontology: SO:0001587]

Functional consequence:

unknown functional consequence

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000577073	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Nov 22, 2018)	germline	clinical testing	Citation Link,
SCV002023792	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 20, 2023)	germline	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

SCV000577073

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Nov 22, 2018)

germline

clinical testing

Citation Link,

SCV002023792

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 20, 2023)

germline

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 GeneDx, SCV000577073.4

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

Description

The R40X pathogenic variant in the GAA gene has been reported previously in multiple individuals with glycogen storage disease type II in the homozygous state, as well as in the heterozygous state in the presence of a second GAA variant (McCready et al., 2007; Sampaolo et al., 2013; Reuser et al., 1995). Additionally, functional studies in transfected COS cells and patient fibroblast cells showed that R40X resulted in reduced enzyme activity and impacts the function of the protein (Reuser et al., 1995). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We interpret R40X as a pathogenic variant.

#	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 Revvity Omics, Revvity, SCV002023792.3

#	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	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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