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NM_000152.5(GAA):c.236_246del (p.Pro79fs) AND Glycogen storage disease, type II

Germline classification:
Pathogenic (4 submissions)
Last evaluated:
Jun 16, 2020
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV000409689.10

Allele description [Variation Report for NM_000152.5(GAA):c.236_246del (p.Pro79fs)]

NM_000152.5(GAA):c.236_246del (p.Pro79fs)

Gene:
GAA:alpha glucosidase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
17q25.3
Genomic location:
Preferred name:
NM_000152.5(GAA):c.236_246del (p.Pro79fs)
HGVS:
  • NC_000017.11:g.80104822_80104832del
  • NG_009822.1:g.8267_8277del
  • NM_000152.5:c.236_246delMANE SELECT
  • NM_001079803.3:c.236_246del
  • NM_001079804.3:c.236_246del
  • NP_000143.2:p.Pro79fs
  • NP_001073271.1:p.Pro79fs
  • NP_001073272.1:p.Pro79fs
  • LRG_673t1:c.236_246del
  • LRG_673t1:c.236_246del11
  • LRG_673:g.8267_8277del
  • NC_000017.10:g.78078615_78078625del
  • NC_000017.10:g.78078621_78078631del
  • NM_000152.3:c.236_246del11
  • NM_000152.5(GAA):c.236_246delMANE SELECT
  • p.Pro79fs
Protein change:
P79fs
Links:
dbSNP: rs1057517165
NCBI 1000 Genomes Browser:
rs1057517165
Molecular consequence:
  • NM_000152.5:c.236_246del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001079803.3:c.236_246del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001079804.3:c.236_246del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Glycogen storage disease, type II (GSD2)
Synonyms:
ACID ALPHA-GLUCOSIDASE DEFICIENCY; GLYCOGENOSIS, GENERALIZED, CARDIAC FORM; GSD II; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009290; MedGen: C0017921; Orphanet: 365; OMIM: 232300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000486851Counsyl
criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))
Pathogenic
(Aug 23, 2016)
unknownclinical testing

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

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV001443298ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel
reviewed by expert panel

(ClinGen LSD ACMG Specifications v1)
Pathogenic
(Jun 16, 2020)
germlinecuration

PubMed (12)
[See all records that cite these PMIDs]

Citation Link,

SCV003442414Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Jan 22, 2024)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004195512Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Pathogenic
(Jan 18, 2024)
unknownclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Post-mortem diagnosis of Pompe disease by exome sequencing in a Moroccan family: a case report.

Adadi N, Sahli M, Egéa G, Ratbi I, Taoudi M, Zniber L, Jdioui W, El Mouatassim S, Sefiani A.

J Med Case Rep. 2018 Oct 29;12(1):322. doi: 10.1186/s13256-018-1855-0.

PubMed [citation]
PMID:
30371346
PMCID:
PMC6205784

Targeted screening for the detection of Pompe disease in patients with unclassified limb-girdle muscular dystrophy or asymptomatic hyperCKemia using dried blood: A Spanish cohort.

Gutiérrez-Rivas E, Bautista J, Vílchez JJ, Muelas N, Díaz-Manera J, Illa I, Martínez-Arroyo A, Olivé M, Sanz I, Arpa J, Fernández-Torrón R, López de Munáin A, Jiménez L, Solera J, Lukacs Z.

Neuromuscul Disord. 2015 Jul;25(7):548-53. doi: 10.1016/j.nmd.2015.04.008. Epub 2015 Apr 23.

PubMed [citation]
PMID:
25998610
See all PubMed Citations (16)

Details of each submission

From Counsyl, SCV000486851.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From ClinGen Lysosomal Storage Disorder Variant Curation Expert Panel, SCV001443298.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (12)

Description

This variant, c.236_246del (p.Pro79ArgfsTer13), has been reported in multiple patients with Pompe disease. For two of these patients, residual GAA activity is reported and meets the ClinGen LSD VCEP's specifications for PP4 (PMID 17056254, 30778879). Both of these patients are compound heterozygous for the variant and a unique pathogenic variant; one with c.377G>A (p.Trp126Ter), in trans (PMID 17056254), and the other with c.1655T>C (p.Leu552Pro), phase unknown (PMID 30778879). This data meets PM3. Additional cases, both homozygous and compound heterozygous, have been reported but were not included because the residual GAA activity was not provided, and therefore PP4 cannot be assessed (PMIDs, 19588081, 22194990, 22980766, 23825616, 25998610, 26913919, 29143201, 30022036, 32125626). There is a ClinVar entry for this variant (Variation ID: 371302, 1 star review status) with 1 submitter classifying the variant as pathogenic. In summary, this variant meets the criteria to be classified as pathogenic for Pompe disease. GAA-specific ACMG/AMP criteria applied, as specified by the ClinGen LSD VCEP: PVS1, PM2, PM3, PP4.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003442414.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Pro79Argfs*13) in the GAA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GAA are known to be pathogenic (PMID: 18425781, 22252923). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Pompe disease (PMID: 17056254). ClinVar contains an entry for this variant (Variation ID: 371302). For these reasons, this variant has been classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Baylor Genetics, SCV004195512.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024