NM_002294.3(LAMP2):c.52T>C (p.Cys18Arg) AND Danon disease

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 28, 2023
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:: RCV003622203.2

Allele description [Variation Report for NM_002294.3(LAMP2):c.52T>C (p.Cys18Arg)]

NM_002294.3(LAMP2):c.52T>C (p.Cys18Arg)

Gene:

LAMP2:lysosomal associated membrane protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq24

Genomic location:

Preferred name:

NM_002294.3(LAMP2):c.52T>C (p.Cys18Arg)

HGVS:

NC_000023.11:g.120469118A>G
NG_007995.1:g.5232T>C
NM_001122606.1:c.52T>C
NM_002294.3:c.52T>CMANE SELECT
NM_013995.2:c.52T>C
NP_001116078.1:p.Cys18Arg
NP_002285.1:p.Cys18Arg
NP_002285.1:p.Cys18Arg
NP_054701.1:p.Cys18Arg
LRG_749t1:c.52T>C
LRG_749t2:c.52T>C
LRG_749t3:c.52T>C
LRG_749:g.5232T>C
LRG_749p1:p.Cys18Arg
LRG_749p2:p.Cys18Arg
LRG_749p3:p.Cys18Arg
NC_000023.10:g.119602973A>G
NM_002294.2:c.52T>C

Protein change:

C18R

Molecular consequence:

NM_001122606.1:c.52T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_002294.3:c.52T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_013995.2:c.52T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Danon disease
Synonyms:: PSEUDOGLYCOGENOSIS II; GSD IIb; LYSOSOMAL GLYCOGEN STORAGE DISEASE WITHOUT ACID MALTASE DEFICIENCY; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010281; MedGen: C0878677; Orphanet: 34587; OMIM: 300257

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004539590	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 28, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29637036, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004539590

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 28, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

A Mild Version of Danon Disease Caused by a Newly Recognized Mutation in the Lysosome-associated Membrane Protein-2 Gene.

Kyaw H, Shaik F, Lin AN, Shinnar M.

Cureus. 2018 Feb 4;10(2):e2155. doi: 10.7759/cureus.2155.

PubMed [citation]

PMID:: 29637036
PMCID:: PMC5884579

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, SCV004539590.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This missense change has been observed in individual(s) with Danon disease (PMID: 29637036). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 18 of the LAMP2 protein (p.Cys18Arg).

#	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

ClinVar

Relating variation to medicine