NM_000152.5(GAA):c.1755-18T>C AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Aug 22, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000438385.3

Allele description [Variation Report for NM_000152.5(GAA):c.1755-18T>C]

NM_000152.5(GAA):c.1755-18T>C

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.1755-18T>C
HGVS:
  • NC_000017.11:g.80112560T>C
  • NG_009822.1:g.16005T>C
  • NM_000152.5:c.1755-18T>CMANE SELECT
  • NM_001079803.3:c.1755-18T>C
  • NM_001079804.3:c.1755-18T>C
  • LRG_673t1:c.1755-18T>C
  • LRG_673:g.16005T>C
  • NC_000017.10:g.78086359T>C
  • NM_000152.3:c.1755-18T>C
  • NM_000152.4:c.1755-18T>C
Links:
dbSNP: rs201399518
NCBI 1000 Genomes Browser:
rs201399518
Molecular consequence:
  • NM_000152.5:c.1755-18T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001079803.3:c.1755-18T>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001079804.3:c.1755-18T>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000518675GeneDxcriteria provided, single submitter
Likely benign
(Nov 7, 2017)
germlineclinical testing

Citation Link,

SCV001361270Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Aug 22, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000518675.4

#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, SCV001361270.1

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

Description

Variant summary: GAA c.1755-18T>C 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. 5/5 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 0.00073 in 247086 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than expected for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) (0.00073 vs 0.0042), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1755-18T>C in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Jun 14, 2021

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