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NM_000152.5(GAA):c.2182T>C (p.Phe728Leu) AND Glycogen storage disease, type II

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Sep 1, 2021
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:
RCV000703619.5

Allele description [Variation Report for NM_000152.5(GAA):c.2182T>C (p.Phe728Leu)]

NM_000152.5(GAA):c.2182T>C (p.Phe728Leu)

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.2182T>C (p.Phe728Leu)
HGVS:
  • NC_000017.11:g.80113359T>C
  • NG_009822.1:g.16804T>C
  • NM_000152.5:c.2182T>CMANE SELECT
  • NM_001079803.3:c.2182T>C
  • NM_001079804.3:c.2182T>C
  • NP_000143.2:p.Phe728Leu
  • NP_001073271.1:p.Phe728Leu
  • NP_001073272.1:p.Phe728Leu
  • LRG_673t1:c.2182T>C
  • LRG_673:g.16804T>C
  • NC_000017.10:g.78087158T>C
  • NM_000152.3:c.2182T>C
Protein change:
F728L
Links:
dbSNP: rs1232306443
NCBI 1000 Genomes Browser:
rs1232306443
Molecular consequence:
  • NM_000152.5:c.2182T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079803.3:c.2182T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079804.3:c.2182T>C - missense variant - [Sequence Ontology: SO:0001583]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000832527Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 1, 2021) 		germlineclinical testing

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

SCV002092109Natera, Inc.
no assertion criteria provided
Uncertain significance
(Dec 17, 2020) 		germlineclinical testing

Help

Summary from all submissions

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

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000832527.2

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

Description

This sequence change replaces phenylalanine with leucine at codon 728 of the GAA protein (p.Phe728Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with GAA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

From Natera, Inc., SCV002092109.1

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

Last Updated: Sep 29, 2024