NM_002294.3(LAMP2):c.183_183+4del AND Danon disease

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 11, 2024
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:: RCV003510718.2

Allele description [Variation Report for NM_002294.3(LAMP2):c.183_183+4del]

NM_002294.3(LAMP2):c.183_183+4del

Gene:

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

Variant type:

Deletion

Cytogenetic location:

Xq24

Genomic location:

Preferred name:

NM_002294.3(LAMP2):c.183_183+4del

HGVS:

NC_000023.11:g.120456648_120456652del
NG_007995.1:g.17699_17703del
NM_001122606.1:c.183_183+4del
NM_002294.3:c.183_183+4delMANE SELECT
NM_013995.2:c.183_183+4del
LRG_749t2:c.183_183+4del
LRG_749t3:c.183_183+4del
LRG_749:g.17699_17703del
NC_000023.10:g.119590502_119590506del
NC_000023.10:g.119590503_119590507del

Molecular consequence:

NM_001122606.1:c.183_183+4del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_002294.3:c.183_183+4del - splice donor variant - [Sequence Ontology: SO:0001575]
NM_013995.2:c.183_183+4del - splice donor variant - [Sequence Ontology: SO:0001575]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004262192	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 11, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16199547, 21415759, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004262192

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 11, 2024)

germline

clinical testing

PubMed (3)
[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

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Natural history of Danon disease.

Boucek D, Jirikowic J, Taylor M.

Genet Med. 2011 Jun;13(6):563-8. doi: 10.1097/GIM.0b013e31820ad795.

PubMed [citation]

PMID:: 21415759

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004262192.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant results in the deletion of part of exon 2 (c.183_183+4del) of the LAMP2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in LAMP2 are known to be pathogenic (PMID: 21415759). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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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