NM_002294.3(LAMP2):c.129T>A (p.Tyr43Ter) AND Danon disease

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 24, 2021
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:: RCV002941902.2

Allele description [Variation Report for NM_002294.3(LAMP2):c.129T>A (p.Tyr43Ter)]

NM_002294.3(LAMP2):c.129T>A (p.Tyr43Ter)

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.129T>A (p.Tyr43Ter)

HGVS:

NC_000023.11:g.120456705A>T
NG_007995.1:g.17645T>A
NM_001122606.1:c.129T>A
NM_002294.3:c.129T>AMANE SELECT
NM_013995.2:c.129T>A
NP_001116078.1:p.Tyr43Ter
NP_002285.1:p.Tyr43Ter
NP_002285.1:p.Tyr43Ter
NP_054701.1:p.Tyr43Ter
LRG_749t1:c.129T>A
LRG_749t2:c.129T>A
LRG_749t3:c.129T>A
LRG_749:g.17645T>A
LRG_749p1:p.Tyr43Ter
LRG_749p2:p.Tyr43Ter
LRG_749p3:p.Tyr43Ter
NC_000023.10:g.119590560A>T
NM_002294.2:c.129T>A

Protein change:

Y43*

Molecular consequence:

NM_001122606.1:c.129T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_002294.3:c.129T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_013995.2:c.129T>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV003268260	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 24, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21415759, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003268260

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 24, 2021)

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

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

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003268260.2

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

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with LAMP2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr43*) in the LAMP2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LAMP2 are known to be pathogenic (PMID: 21415759).

#	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: Feb 20, 2024

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