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NM_000152.5(GAA):c.2481+16G>A AND not specified

Germline classification:
Likely benign (2 submissions)
Last evaluated:
Jul 1, 2021
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:
RCV000078173.8

Allele description [Variation Report for NM_000152.5(GAA):c.2481+16G>A]

NM_000152.5(GAA):c.2481+16G>A

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.2481+16G>A
HGVS:
  • NC_000017.11:g.80117765G>A
  • NG_009822.1:g.21210G>A
  • NM_000152.5:c.2481+16G>AMANE SELECT
  • NM_001079803.3:c.2481+16G>A
  • NM_001079804.3:c.2481+16G>A
  • LRG_673t1:c.2481+16G>A
  • LRG_673:g.21210G>A
  • NC_000017.10:g.78091564G>A
  • NM_000152.3:c.2481+16G>A
  • NM_000152.4(GAA):c.2481+16G>A
  • NM_000152.4:c.2481+16G>A
Links:
dbSNP: rs41292408
NCBI 1000 Genomes Browser:
rs41292408
Molecular consequence:
  • NM_000152.5:c.2481+16G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001079803.3:c.2481+16G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001079804.3:c.2481+16G>A - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000519706GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Likely benign
(Jun 13, 2017) 		germlineclinical testing

Citation Link,

SCV001748802Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely benign
(Jul 1, 2021) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The Latin American experience with a next generation sequencing genetic panel for recessive limb-girdle muscular weakness and Pompe disease.

Bevilacqua JA, Guecaimburu Ehuletche MDR, Perna A, Dubrovsky A, Franca MC Jr, Vargas S, Hegde M, Claeys KG, Straub V, Daba N, Faria R, Periquet M, Sparks S, Thibault N, Araujo R.

Orphanet J Rare Dis. 2020 Jan 13;15(1):11. doi: 10.1186/s13023-019-1291-2.

PubMed [citation]
PMID:
31931849
PMCID:
PMC6958675

Details of each submission

From GeneDx, SCV000519706.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001748802.1

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

Description

Variant summary: GAA c.2481+16G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0023 in 219566 control chromosomes, predominantly at a frequency of 0.0038 within the Non-Finnish European subpopulation in the gnomAD database, including 2 homozygotes. The frequency within the Non-Finnish European subpopulation is very close to the maximum frequency expected for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) (0.0038 vs 0.0042), suggesting a possible benign role for the variant. To our knowledge, no occurrence of c.2481+16G>A in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as benign (n=1), likely benign (n=3), and uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Oct 13, 2024