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NM_000152.5(GAA):c.725C>T (p.Ala242Val) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 20, 2019
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000770759.2

Allele description [Variation Report for NM_000152.5(GAA):c.725C>T (p.Ala242Val)]

NM_000152.5(GAA):c.725C>T (p.Ala242Val)

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.725C>T (p.Ala242Val)
HGVS:
  • NC_000017.11:g.80107589C>T
  • NG_009822.1:g.11034C>T
  • NM_000152.5:c.725C>TMANE SELECT
  • NM_001079803.3:c.725C>T
  • NM_001079804.3:c.725C>T
  • NP_000143.2:p.Ala242Val
  • NP_001073271.1:p.Ala242Val
  • NP_001073272.1:p.Ala242Val
  • LRG_673t1:c.725C>T
  • LRG_673:g.11034C>T
  • NC_000017.10:g.78081388C>T
  • NM_000152.3:c.725C>T
  • NM_000152.4:c.725C>T
Protein change:
A242V
Links:
dbSNP: rs745861849
NCBI 1000 Genomes Browser:
rs745861849
Molecular consequence:
  • NM_000152.5:c.725C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079803.3:c.725C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079804.3:c.725C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000695665Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Feb 20, 2019) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

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

Citations

PubMed

Update of the Pompe disease mutation database with 107 sequence variants and a format for severity rating.

Kroos M, Pomponio RJ, van Vliet L, Palmer RE, Phipps M, Van der Helm R, Halley D, Reuser A; GAA Database Consortium..

Hum Mutat. 2008 Jun;29(6):E13-26. doi: 10.1002/humu.20745.

PubMed [citation]
PMID:
18425781

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000695665.3

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

Description

Variant summary: GAA c.725C>T (p.Ala242Val) results in a non-conservative amino acid change located in the Galactose mutarotase, N-terminal barrel domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 9.3e-05 in 246022 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) (9.3e-05 vs 0.0042), allowing no conclusion about variant significance. c.725C>T has been reported in the literature in an affected individual (Kroos_2008). This report does not provide unequivocal conclusions about association of the variant with Glycogen Storage Disease, Type 2 (Pompe Disease). Experimental evidence evaluating an impact on protein function demonstrated a potentially mild effect on alpha-glucosidase activity (Kroos_2008). Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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

Last Updated: Sep 29, 2024