NM_000152.5(GAA):c.2266C>T (p.Leu756Phe) AND Glycogen storage disease, type II

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 30, 2022
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:: RCV003052773.2

Allele description [Variation Report for NM_000152.5(GAA):c.2266C>T (p.Leu756Phe)]

NM_000152.5(GAA):c.2266C>T (p.Leu756Phe)

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.2266C>T (p.Leu756Phe)

HGVS:

NC_000017.11:g.80117044C>T
NG_009822.1:g.20489C>T
NM_000152.5:c.2266C>TMANE SELECT
NM_001079803.3:c.2266C>T
NM_001079804.3:c.2266C>T
NM_001406741.1:c.2266C>T
NM_001406742.1:c.2266C>T
NP_000143.2:p.Leu756Phe
NP_000143.2:p.Leu756Phe
NP_001073271.1:p.Leu756Phe
NP_001073272.1:p.Leu756Phe
NP_001393670.1:p.Leu756Phe
NP_001393671.1:p.Leu756Phe
LRG_673t1:c.2266C>T
LRG_673:g.20489C>T
LRG_673p1:p.Leu756Phe
NC_000017.10:g.78090843C>T
NM_000152.3:c.2266C>T

Protein change:

L756F

Molecular consequence:

NM_000152.5:c.2266C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001079803.3:c.2266C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001079804.3:c.2266C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406741.1:c.2266C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001406742.1:c.2266C>T - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003444940	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 30, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003444940

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 30, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV003444940.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 756 of the GAA protein (p.Leu756Phe). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with GAA-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GAA protein function. 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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