Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_002294.3(LAMP2):c.121delT(p.Cys41AlafsTer8) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. C41C) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )

Failed GnomAD Quality Control

Consequence

LAMP2
NM_002294.3 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 5.70

Publications

2 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: Pathogenic. The variant received 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant X-120456712-CA-C is Pathogenic according to our data. Variant chrX-120456712-CA-C is described in ClinVar as Pathogenic. ClinVar VariationId is 179062.Status of the report is criteria_provided_single_submitter, 1 stars.

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	HGVSp	Effect	Exon Rank	Protein
LAMP2	NM_002294.3	MANE Select	c.121delT	p.Cys41AlafsTer8	frameshift	Exon 2 of 9	NP_002285.1
LAMP2	NM_001122606.1		c.121delT	p.Cys41AlafsTer8	frameshift	Exon 2 of 9	NP_001116078.1
LAMP2	NM_013995.2		c.121delT	p.Cys41AlafsTer8	frameshift	Exon 2 of 9	NP_054701.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
LAMP2	ENST00000200639.9	TSL:1 MANE Select	c.121delT	p.Cys41AlafsTer8	frameshift	Exon 2 of 9	ENSP00000200639.4
LAMP2	ENST00000434600.6	TSL:1	c.121delT	p.Cys41AlafsTer8	frameshift	Exon 2 of 9	ENSP00000408411.2
LAMP2	ENST00000371335.4	TSL:1	c.121delT	p.Cys41AlafsTer8	frameshift	Exon 2 of 9	ENSP00000360386.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1080686

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

349648

African (AFR)

AF:

0.00

AC:

AN:

26137

American (AMR)

AF:

0.00

AC:

AN:

35051

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19203

East Asian (EAS)

AF:

0.00

AC:

AN:

29989

South Asian (SAS)

AF:

0.00

AC:

AN:

52164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40142

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3347

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

829324

Other (OTH)

AF:

0.00

AC:

AN:

45329

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Danon disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

5.7

Mutation Taster

=0/200

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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.

NM_002294.3:c.121delT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over