NM_000152.5(GAA):c.2238G>A (p.Trp746Ter) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 22, 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:: RCV000723386.12

Allele description [Variation Report for NM_000152.5(GAA):c.2238G>A (p.Trp746Ter)]

NM_000152.5(GAA):c.2238G>A (p.Trp746Ter)

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.2238G>A (p.Trp746Ter)

HGVS:

NC_000017.11:g.80117016G>A
NG_009822.1:g.20461G>A
NM_000152.3(GAA):c.2238G>A
NM_000152.5:c.2238G>AMANE SELECT
NM_001079803.3:c.2238G>A
NM_001079804.3:c.2238G>A
NP_000143.2:p.Trp746Ter
NP_001073271.1:p.Trp746Ter
NP_001073272.1:p.Trp746Ter
LRG_673t1:c.2238G>A
LRG_673:g.20461G>A
NC_000017.10:g.78090815G>A
NM_000152.3(GAA):c.2238G>A
NM_000152.3:c.2238G>A
NM_000152.4:c.2238G>A
NM_000152.5:c.2238G>A
p.Trp746Ter

Protein change:

W746*

Links:

dbSNP: rs1800312

NCBI 1000 Genomes Browser:

rs1800312

Molecular consequence:

NM_000152.5:c.2238G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001079803.3:c.2238G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001079804.3:c.2238G>A - nonsense - [Sequence Ontology: SO:0001587]

Observations:

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
SCV000700286	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Jan 17, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16860134, 23430493 Citation Link,
SCV000890192	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 9, 2021)	germline	clinical testing	Citation Link,
SCV002023836	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 22, 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

SCV000700286

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Jan 17, 2017)

germline

clinical testing

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

Citation Link,

SCV000890192

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Dec 9, 2021)

germline

clinical testing

Citation Link,

SCV002023836

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jun 22, 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease.

Kishnani PS, Nicolino M, Voit T, Rogers RC, Tsai AC, Waterson J, Herman GE, Amalfitano A, Thurberg BL, Richards S, Davison M, Corzo D, Chen YT.

J Pediatr. 2006 Jul;149(1):89-97.

PubMed [citation]

PMID:: 16860134
PMCID:: PMC2692727

Identification and Functional Characterization of GAA Mutations in Colombian Patients Affected by Pompe Disease.

Niño MY, Mateus HE, Fonseca DJ, Kroos MA, Ospina SY, Mejía JF, Uribe JA, Reuser AJ, Laissue P.

JIMD Rep. 2013;7:39-48. doi: 10.1007/8904_2012_138. Epub 2012 Apr 19.

PubMed [citation]

PMID:: 23430493
PMCID:: PMC3575054

See all PubMed Citations (3)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000700286.2

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

#	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	not provided	not provided

From GeneDx, SCV000890192.3

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

Description

Published functional studies demonstrate the variant results in reduced GAA activity (Nino et al., 2013); Not observed at a significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 26889246, 22613277, 25525159, 23457621, 22252923, 25741864, 26685070, 18519449, 29880332, 29122469, 10206684, 28726123, 33741225, 27655474, 26497565, 16860134, 23430493)

#	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, SCV002023836.3

#	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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