NM_000152.5(GAA):c.2580C>T (p.Asp860=) AND not specified

Clinical significance:Benign/Likely benign (Last evaluated: Mar 11, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000314439.5

Allele description [Variation Report for NM_000152.5(GAA):c.2580C>T (p.Asp860=)]

NM_000152.5(GAA):c.2580C>T (p.Asp860=)

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.2580C>T (p.Asp860=)
HGVS:
  • NC_000017.11:g.80118291C>T
  • NG_009822.1:g.21736C>T
  • NM_000152.5:c.2580C>TMANE SELECT
  • NM_001079803.3:c.2580C>T
  • NM_001079804.3:c.2580C>T
  • NP_000143.2:p.Asp860=
  • NP_001073271.1:p.Asp860=
  • NP_001073272.1:p.Asp860=
  • LRG_673t1:c.2580C>T
  • LRG_673:g.21736C>T
  • NC_000017.10:g.78092090C>T
  • NM_000152.3:c.2580C>T
  • NM_000152.4:c.2580C>T
Links:
dbSNP: rs61736894
NCBI 1000 Genomes Browser:
rs61736894
Molecular consequence:
  • NM_000152.5:c.2580C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001079803.3:c.2580C>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001079804.3:c.2580C>T - synonymous variant - [Sequence Ontology: SO:0001819]
Observations:
1

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
SCV000332714EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Benign
(Jul 30, 2015)
germlineclinical testing

Citation Link,

SCV000522329GeneDxcriteria provided, single submitter
Likely benign
(Sep 5, 2017)
germlineclinical testing

Citation Link,

SCV001361268Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Benign
(Mar 11, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical testing

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000332714.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From GeneDx, SCV000522329.4

#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, SCV001361268.1

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

Description

Variant summary: GAA c.2580C>T alters a non-conserved nucleotide resulting in a synonymous change. 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 0.0014 in 263280 control chromosomes, predominantly at a frequency of 0.015 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 4-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) phenotype (0.0042), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.2580C>T in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submission from clinical diagnostic laboratories (evaluation after 2014) cite the variant twice as likely benign and twice as benign. Based on the evidence outlined above, the variant was classified as benign.

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

Last Updated: Jun 14, 2021

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