VCV000004031.3 - ClinVar

NM_000152.5(GAA):c.2483_2646+1del

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(2)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Pathogenic

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000152.5(GAA):c.2483_2646+1del

Variation ID: 4031 Accession: VCV000004031.3

Type and length

Deletion, 165 bp

Location

Cytogenetic: 17q25.3 17: 80118193-80118357 (GRCh38) [ NCBI UCSC ] 17: 78091992-78092156 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 2, 2013	Oct 1, 2022	Mar 1, 1998

HGVS

Nucleotide	Protein	Molecular consequence
NM_000152.5:c.2483_2646+1del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.		splice donor
NM_001079803.3:c.2483_2646+1del		splice donor
NM_001079804.3:c.2483_2646+1del		splice donor
NC_000017.11:g.80118194_80118358del
NC_000017.10:g.78091993_78092157del
NG_009822.1:g.21639_21803del
LRG_673:g.21639_21803del

... more HGVS ... less HGVS

Protein change

Other names

Exon 18 del
EX18DEL

Canonical SPDI

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA340127 OMIM: 606800.0012 dbSNP: rs1555603048 VarSome

Comment on variant

NCBI reports the breakpoints for the deletion as defined by the GAA LSDB, GAA_00037

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
GAA		-	-	GRCh38 GRCh38 GRCh37	2805	2857

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Glycogen storage disease, type II	Pathogenic (2)	no assertion criteria provided	Mar 1, 1998	RCV000004246.7

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Pathogenic (Mar 01, 1998)	no assertion criteria provided Method: literature only	GLYCOGEN STORAGE DISEASE II Affected status: not provided Allele origin: germline	OMIM Accession: SCV000024412.3 First in ClinVar: Apr 04, 2013 Last updated: Oct 23, 2017	Publications: PubMed (5) PubMed: 7945303‚ 7881425‚ 10737124‚ 7717400‚ 8990003 Comment on evidence: Van der Kraan et al. (1994) reported that deletion of exon 18 of the GAA gene is a frequent mutation in Pompe disease (GSD2; 232300). … (more) Van der Kraan et al. (1994) reported that deletion of exon 18 of the GAA gene is a frequent mutation in Pompe disease (GSD2; 232300). Huie et al. (1994) found this mutation in patients with both infantile and adult forms of this disease. Vorgerd et al. (1998) found homozygosity for the exon 18 deletion in 2 affected sibs and an unrelated patient with adult-type GSD II. Boerkoel et al. (1995) found a deletion of exon 18 of the GAA gene in 3 unrelated compound heterozygous patients, 2 of whom were infants, and 1 an adult. The second mutation in each of these patients was different. The infants with Pompe disease were French Canadian and Dutch. The adult was a woman of German extraction who had first consulted her physician at age 39 years for progressive proximal muscle weakness and respiratory insufficiency. In retrospect, she could recall limitation in her activity as far back as early adulthood. In one of the infants, there was deletion of lys903 (606800.0007); in the other, there was a leu299-to-arg substitution (606800.0008). In the adult, the authors observed a T-to-G transversion at position -13 of intron 1 (606800.0006). Although Kroos et al. (1995) found deletion of exon 18 in the infantile and adult forms of the disease, those homozygous for this mutation and heterozygous for this mutation in combination with deletion of 525T (606800.0014) had the infantile form of Pompe disease; however, patients with deletion of exon 18 or deletion of 525T in combination with transversion of T to G at position -13 (606800.0006) had the juvenile or the adult form, suggesting that the intronic mutation was a mild mutation. (less)
not provided (-)	no classification provided Method: literature only	Glycogen storage disease, type II Affected status: unknown Allele origin: germline	GeneReviews Accession: SCV000086727.3 First in ClinVar: Oct 02, 2013 Last updated: Oct 01, 2022	Publications: PubMed (1) PubMed: 20301438 BookShelf: NBK1261 BookShelf: NBK1261

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Pompe Disease.	Adam MP	-	2023	PMID: 20301438
Adult-onset glycogen storage disease type II: phenotypic and allelic heterogeneity in German patients.	Vorgerd M	Neurogenetics	1998	PMID: 10737124
Two extremes of the clinical spectrum of glycogen storage disease type II in one family: a matter of genotype.	Kroos MA	Human mutation	1997	PMID: 8990003
Leaky splicing mutation in the acid maltase gene is associated with delayed onset of glycogenosis type II.	Boerkoel CF	American journal of human genetics	1995	PMID: 7717400
Deletion of exon 18 is a frequent mutation in glycogen storage disease type II.	Van der Kraan M	Biochemical and biophysical research communications	1994	PMID: 7945303
Aberrant splicing in adult onset glycogen storage disease type II (GSDII): molecular identification of an IVS1 (-13T-->G) mutation in a majority of patients and a novel IVS10 (+1GT-->CT) mutation.	Huie ML	Human molecular genetics	1994	PMID: 7881425

Text-mined citations for rs1555603048 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Mar 18, 2023

ClinVar Genomic variation as it relates to human health

NM_000152.5(GAA):c.2483_2646+1del

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1555603048 ...