VCV000180889.12 - ClinVar

NM_002294.3(LAMP2):c.1114GAC[1] (p.Asp373del)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance (1); Likely benign (1)

2 out of 3 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_002294.3(LAMP2):c.1114GAC[1] (p.Asp373del)

Variation ID: 180889 Accession: VCV000180889.12

Type and length

Microsatellite, 3 bp

Location

Cytogenetic: Xq24 X: 120431437-120431439 (GRCh38) [ NCBI UCSC ] X: 119565292-119565294 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Jul 24, 2016	Feb 23, 2026	Jan 26, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_002294.3:c.1114GAC[1] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_002285.1:p.Asp373del	inframe deletion
NM_001122606.1:c.1094-2813_1094-2811del		intron variant
NM_002294.2:c.1117_1119delGAC
NC_000023.11:g.120431437GTC[1]
NC_000023.10:g.119565292GTC[1]
NG_007995.1:g.42908GAC[1]
LRG_749:g.42908GAC[1]
LRG_749t3:c.1094-2813_1094-2811del

... more HGVS ... less HGVS

Protein change

D373del

Other names

Canonical SPDI

NC_000023.11:120431436:GTCGTC:GTC

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA333711 dbSNP: rs730880494 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
LAMP2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	955	1133

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not provided	Uncertain significance (1)	criteria provided, single submitter	Jun 28, 2016	RCV000157987.2
Danon disease	Likely benign (1)	criteria provided, single submitter	Jan 26, 2026	RCV001401384.9
LAMP2-related disorder	Likely benign (1)	no assertion criteria provided	Sep 5, 2020	RCV003945250.2

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Jun 28, 2016) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015))	not provided	GeneDx Accession: SCV000207922.13 First in ClinVar: Feb 24, 2015 Last updated: Jul 24, 2016	Comment: show The c.1117_1119delGAC variant has been reported previously in a male patient with accessory atrioventricular connection and it also was identified in his unaffected mother and brother (Esposito G et al., 2009). The authors hypothesized that the loss of the Aspartic Acid residue at this position (the P5 substrate position") might be critical for proteolytic regulation of LAMP-2. Additionally, it was not identified in 600 control chromosomes from Caucasian individuals, indicating it is not a common benign variant in this population. However, the lack of segregation with a disease phenotype in the published family suggests further studies are needed to determine the pathogenic role of this variant. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant." (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely benign (Jan 26, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Danon disease	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001603207.6 First in ClinVar: May 16, 2021 Last updated: Feb 23, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Sep 05, 2020) N Not contributing to aggregate classification	no assertion criteria provided	LAMP2-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004769809.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

The c.1117_1119delGAC variant has been reported previously in a male patient with accessory atrioventricular connection and it also was identified in his unaffected mother and brother (Esposito G et al., 2009). The authors hypothesized that the loss of the Aspartic Acid residue at this position (the P5 substrate position") might be critical for proteolytic regulation of LAMP-2. Additionally, it was not identified in 600 control chromosomes from Caucasian individuals, indicating it is not a common benign variant in this population. However, the lack of segregation with a disease phenotype in the published family suggests further studies are needed to determine the pathogenic role of this variant. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant."

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs730880494 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 13, 2026