NM_000152.5(GAA):c.2237G>C (p.Trp746Ser) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 20, 2022
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:: RCV001781520.13

Allele description [Variation Report for NM_000152.5(GAA):c.2237G>C (p.Trp746Ser)]

NM_000152.5(GAA):c.2237G>C (p.Trp746Ser)

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.2237G>C (p.Trp746Ser)

HGVS:

NC_000017.11:g.80117015G>C
NG_009822.1:g.20460G>C
NM_000152.5:c.2237G>CMANE SELECT
NM_001079803.2(GAA):c.2237G>C
NM_001079803.3:c.2237G>C
NM_001079804.3:c.2237G>C
NP_000143.2:p.Trp746Ser
NP_001073271.1:p.Trp746Ser
NP_001073272.1:p.Trp746Ser
LRG_673t1:c.2237G>C
LRG_673:g.20460G>C
NC_000017.10:g.78090814G>C
NM_000152.3:c.2237G>C
NM_000152.4:c.2237G>C
NM_001079803.2(GAA):c.2237G>C
NM_001079803.2:c.2237G>C
P10253:p.Trp746Ser

Protein change:

W746S

Links:

UniProtKB: P10253#VAR_068632; dbSNP: rs752921215

NCBI 1000 Genomes Browser:

rs752921215

Molecular consequence:

NM_000152.5:c.2237G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001079803.3:c.2237G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001079804.3:c.2237G>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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protein unc-80 homolog isoform X12 [Rattus norvegicus]
protein unc-80 homolog isoform X12 [Rattus norvegicus]
gi|1958805107|ref|XP_038940529.1|

Protein
NADH dehydrogenase subunit 6 (mitochondrion) [Apterichtus klazingai]
NADH dehydrogenase subunit 6 (mitochondrion) [Apterichtus klazingai]
gi|2580280160|gb|WNH21308.1|

Protein
Chromosome neighbors for GEO Profiles (Select 77148430) (20)
GEO Profiles
BioAssays, Active for PubChem Compound (Select 91623361) (0)
PubChem BioAssay
Protein Links for Conserved Domains (Select 236686) (4300)
Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002025231	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 20, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002502344	AiLife Diagnostics, AiLife Diagnostics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 23, 2021)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 18425781, 31589614, 29325298, 22644586, 23430493, 30275481, 25741868
SCV002568586	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Apr 1, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002025231

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 20, 2022)

germline

clinical testing

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

SCV002502344

AiLife Diagnostics, AiLife Diagnostics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 23, 2021)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV002568586

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Apr 1, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	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

Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating.

Kroos M, Pomponio RJ, van Vliet L, Palmer RE, Phipps M, Van der Helm R, Halley D, Reuser A; GAA Database Consortium..

Hum Mutat. 2008 Jun;29(6):E13-26. doi: 10.1002/humu.20745.

PubMed [citation]

PMID:: 18425781

Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes.

Capalbo A, Valero RA, Jimenez-Almazan J, Pardo PM, Fabiani M, Jiménez D, Simon C, Rodriguez JM.

PLoS Genet. 2019 Oct;15(10):e1008409. doi: 10.1371/journal.pgen.1008409.

PubMed [citation]

PMID:: 31589614
PMCID:: PMC6797235

See all PubMed Citations (7)

Details of each submission

From Revvity Omics, Revvity, SCV002025231.3

#	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

From AiLife Diagnostics, AiLife Diagnostics, SCV002502344.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (7)

#	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		2	not provided	not provided	not provided

From GeneDx, SCV002568586.2

#	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 that p.(W746S) results in a significant reduction in enzymatic activity (Kroos et al., 2012; Nino et al., 2013); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 24444888, 24169249, 18425781, 22644586, 23430493, 29325298, 30275481, 19343043, 22253258, 31589614, 27535533, 34906458, 26582918, 34020684, 33717985, 22081099, Jian2021, 33344388)

#	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

Last Updated: Sep 29, 2024

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