rs746330494

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2

The NM_002294.3(LAMP2):c.865-8delT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000262 in 1,069,203 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 hemizygotes in GnomAD. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000026 ( 0 hom. 9 hem. )

Failed GnomAD Quality Control

Consequence

LAMP2
NM_002294.3 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 2.87

Publications

0 publications found

Variant links:

Genes affected

LAMP2 (HGNC:6501): (lysosomal associated membrane protein 2) The protein encoded by this gene is a member of a family of membrane glycoproteins. This glycoprotein provides selectins with carbohydrate ligands. It may play a role in tumor cell metastasis. It may also function in the protection, maintenance, and adhesion of the lysosome. Alternative splicing of this gene results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Jul 2008]

LAMP2 Gene-Disease associations (from GenCC):

Danon disease
Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet

LAMP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP6

Variant X-120442669-GA-G is Benign according to our data. Variant chrX-120442669-GA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 415504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Hemizygotes in GnomAdExome4 at 9 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002294.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LAMP2	NM_002294.3	MANE Select	c.865-8delT	splice_region intron	N/A	NP_002285.1
LAMP2	NM_001122606.1		c.865-8delT	splice_region intron	N/A	NP_001116078.1
LAMP2	NM_013995.2		c.865-8delT	splice_region intron	N/A	NP_054701.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
LAMP2	ENST00000200639.9	TSL:1 MANE Select	c.865-8delT	splice_region intron	N/A	ENSP00000200639.4
LAMP2	ENST00000434600.6	TSL:1	c.865-8delT	splice_region intron	N/A	ENSP00000408411.2
LAMP2	ENST00000371335.4	TSL:1	c.865-8delT	splice_region intron	N/A	ENSP00000360386.4

Frequencies

GnomAD3 genomes

AF:

0.00000894

AC:

AN:

111824

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000438

AC:

AN:

182769

AF XY:

0.0000297

show subpopulations

Gnomad AFR exome

AF:

0.0000761

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000857

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000262

AC:

AN:

1069203

Hom.:

Cov.:

AF XY:

0.0000267

AC XY:

AN XY:

336501

show subpopulations

African (AFR)

AF:

0.0000386

AC:

AN:

25876

American (AMR)

AF:

0.00

AC:

AN:

35158

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19197

East Asian (EAS)

AF:

0.00

AC:

AN:

30103

South Asian (SAS)

AF:

0.00

AC:

AN:

53410

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40201

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4060

European-Non Finnish (NFE)

AF:

0.0000331

AC:

AN:

816038

Other (OTH)

AF:

0.00

AC:

AN:

45160

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.459

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000894

AC:

AN:

111824

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34054

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30754

American (AMR)

AF:

0.00

AC:

AN:

10535

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2649

East Asian (EAS)

AF:

0.00

AC:

AN:

3596

South Asian (SAS)

AF:

0.00

AC:

AN:

2699

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6002

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53156

Other (OTH)

AF:

0.00

AC:

AN:

1511

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Apr 24, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: LAMP2 c.865-8delT alters a conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.5e-05 in 1181027 control chromosomes, predominantly at a frequency of 3.2e-05 within the Non-Finnish European subpopulation in the gnomAD database, including 10 hemizygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in LAMP2 causing Danon disease phenotype. To our knowledge, no occurrence of c.865-8delT in individuals affected with Danon disease and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 415504). Based on the evidence outlined above, the variant was classified as benign.

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

not provided

Benign:2

Jan 30, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Danon disease

Benign:1

Oct 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

LAMP2-related disorder

Benign:1

Aug 13, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.9

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over