NM_000152.5(GAA):c.2057_2058delinsAA (p.Ser686Lys) AND Glycogen storage disease, type II

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 31, 2018
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:: RCV000813141.7

Allele description [Variation Report for NM_000152.5(GAA):c.2057_2058delinsAA (p.Ser686Lys)]

NM_000152.5(GAA):c.2057_2058delinsAA (p.Ser686Lys)

Gene:

GAA:alpha glucosidase [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_000152.5(GAA):c.2057_2058delinsAA (p.Ser686Lys)

HGVS:

NC_000017.11:g.80113234_80113235delinsAA
NG_009822.1:g.16679_16680delinsAA
NM_000152.5:c.2057_2058delinsAAMANE SELECT
NM_001079803.3:c.2057_2058delinsAA
NM_001079804.3:c.2057_2058delinsAA
NP_000143.2:p.Ser686Lys
NP_001073271.1:p.Ser686Lys
NP_001073272.1:p.Ser686Lys
LRG_673t1:c.2057_2058delGCinsAA
LRG_673:g.16679_16680delinsAA
NC_000017.10:g.78087033_78087034delinsAA
NM_000152.3:c.2057_2058delGCinsAA

Protein change:

S686K

Links:

dbSNP: rs1598586309

NCBI 1000 Genomes Browser:

rs1598586309

Molecular consequence:

NM_000152.5:c.2057_2058delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_001079803.3:c.2057_2058delinsAA - missense variant - [Sequence Ontology: SO:0001583]
NM_001079804.3:c.2057_2058delinsAA - 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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Mus musculus non imprinted in Prader-Willi/Angelman syndrome 2 homolog (human) (...
Mus musculus non imprinted in Prader-Willi/Angelman syndrome 2 homolog (human) (Nipa2), mRNA
gi|158508633|ref|NM_023647.5|

Nucleotide
ENPP1 [Vulpes lagopus]
ENPP1 [Vulpes lagopus]
Gene ID:121484863

Gene
PGLS [Panthera uncia]
PGLS [Panthera uncia]
Gene ID:125929222

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000953486	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 31, 2018)	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

SCV000953486

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 31, 2018)

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, SCV000953486.3

#	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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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 disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine¬†with lysine¬†at codon 686 of the GAA protein (p.Ser686Lys). The¬†serine¬†residue is weakly conserved and there is a moderate physicochemical difference between¬†serine¬†and lysine.

#	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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