NM_000152.5(GAA):c.2647-20T>G AND not provided

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jan 26, 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:: RCV001816675.5

Allele description [Variation Report for NM_000152.5(GAA):c.2647-20T>G]

NM_000152.5(GAA):c.2647-20T>G

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.2647-20T>G

HGVS:

NC_000017.11:g.80118633T>G
NG_009822.1:g.22078T>G
NM_000152.5:c.2647-20T>GMANE SELECT
NM_001079803.3:c.2647-20T>G
NM_001079804.3:c.2647-20T>G
LRG_673t1:c.2647-20T>G
LRG_673:g.22078T>G
NC_000017.10:g.78092432T>G
NM_000152.3:c.2647-20T>G

Links:

dbSNP: rs1555603208

NCBI 1000 Genomes Browser:

rs1555603208

Molecular consequence:

NM_000152.5:c.2647-20T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001079803.3:c.2647-20T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001079804.3:c.2647-20T>G - intron variant - [Sequence Ontology: SO:0001627]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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rho guanine nucleotide exchange factor 39 [Mus musculus]
rho guanine nucleotide exchange factor 39 [Mus musculus]
gi|225543124|ref|NP_001013395.2|

Protein
Homo sapiens obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF, mRN...
Homo sapiens obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF, mRNA (cDNA clone IMAGE:3845393), with apparent retained intron
gi|27881999|gb|BC043916.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002065879	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Sep 17, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004225027	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 26, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23062590, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002065879

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Sep 17, 2021)

germline

clinical testing

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

SCV004225027

Mayo Clinic Laboratories, Mayo Clinic

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 26, 2023)

germline

clinical testing

PubMed (2)
[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	1	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

Presymptomatic late-onset Pompe disease identified by the dried blood spot test.

Wagner M, Chaouch A, Müller JS, Polvikoski T, Willis TA, Sarkozy A, Eagle M, Bushby K, Straub V, Lochmüller H.

Neuromuscul Disord. 2013 Jan;23(1):89-92. doi: 10.1016/j.nmd.2012.09.004. Epub 2012 Oct 10.

PubMed [citation]

PMID:: 23062590

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 Genetic Services Laboratory, University of Chicago, SCV002065879.1

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

Description

The second sequence change, c.2647-20T>G, occurs in intron 18. This variant is absent from population databases including ExAC and gnomAD. This sequence change has been reported in the compound heterozygous state with the c.-32-13T>G variant in an individual with late-onset Pompe disease (PMID: 23062590). In-silico splice prediction programs predict that this sequence change likely affects normal splicing. Experimental studies demonstrated that this sequence change creates a splice acceptor site 20 bases upstream of exon 19. This leads to an insertion of 20 bases and creates a premature stop codon after 14 bases in exon 19 (PMID: 23062590). Based on these evidences, the c.2647-20T>G variant is classified as likely pathogenic.

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV004225027.1

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

Description

PP3, PP4, PM2_supporting, PM3_supporting, PS3

#	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		1	not provided	not provided	not provided

Last Updated: Jan 6, 2024

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