NM_000152.5(GAA):c.2306T>C (p.Leu769Ser) AND Glycogen storage disease, type II

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jul 19, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001063671.8

Allele description [Variation Report for NM_000152.5(GAA):c.2306T>C (p.Leu769Ser)]

NM_000152.5(GAA):c.2306T>C (p.Leu769Ser)

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.2306T>C (p.Leu769Ser)

HGVS:

NC_000017.11:g.80117084T>C
NG_009822.1:g.20529T>C
NM_000152.5:c.2306T>CMANE SELECT
NM_001079803.3:c.2306T>C
NM_001079804.3:c.2306T>C
NP_000143.2:p.Leu769Ser
NP_001073271.1:p.Leu769Ser
NP_001073272.1:p.Leu769Ser
LRG_673t1:c.2306T>C
LRG_673:g.20529T>C
NC_000017.10:g.78090883T>C
NM_000152.3:c.2306T>C

Protein change:

L769S

Links:

dbSNP: rs2039369551

NCBI 1000 Genomes Browser:

rs2039369551

Molecular consequence:

NM_000152.5:c.2306T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001079803.3:c.2306T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001079804.3:c.2306T>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

Recent activity

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PREDICTED: conserved oligomeric Golgi complex subunit 5-like [Nicotiana tabacum]
PREDICTED: conserved oligomeric Golgi complex subunit 5-like [Nicotiana tabacum]
gi|1025276830|ref|XP_016494429.1|

Protein
Management of Uterine Fibroids
Management of Uterine Fibroids

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001228528	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 4, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002816954	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 19, 2021)	unknown	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

SCV001228528

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 4, 2019)

germline

clinical testing

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

SCV002816954

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 19, 2021)

unknown

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
not provided	unknown	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001228528.5

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with GAA-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with serine at codon 769 of the GAA protein (p.Leu769Ser). The leucine residue is weakly conserved and there is a large physicochemical difference between leucine and serine.

#	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

From Fulgent Genetics, Fulgent Genetics, SCV002816954.1

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

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

Last Updated: Sep 29, 2024

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