rs727504557
Positions:
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_002294.3(LAMP2):c.999del(p.Glu334SerfsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 22)
Consequence
LAMP2
NM_002294.3 frameshift
NM_002294.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.29
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.19 CDS is truncated, and there are 3 pathogenic variants in the truncated region.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant X-120441823-CT-C is Pathogenic according to our data. Variant chrX-120441823-CT-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 178945.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
LAMP2 | NM_002294.3 | c.999del | p.Glu334SerfsTer12 | frameshift_variant | 8/9 | ENST00000200639.9 | |
LAMP2 | NM_001122606.1 | c.999del | p.Glu334SerfsTer12 | frameshift_variant | 8/9 | ||
LAMP2 | NM_013995.2 | c.999del | p.Glu334SerfsTer12 | frameshift_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMP2 | ENST00000200639.9 | c.999del | p.Glu334SerfsTer12 | frameshift_variant | 8/9 | 1 | NM_002294.3 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome ? Cov.: 22
GnomAD4 genome
?
Cov.:
22
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Primary dilated cardiomyopathy Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 27, 2014 | The Glu334fs variant in LAMP2 has now been identified by our laboratory in 1 ind ividual with DCM and ARVC and segregated with disease in 2 affected relatives. I t was absent from large population studies. This frameshift variant is predicted to alter the protein's amino acid sequence beginning at position 334 and lead t o premature termination codon 12 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the LA MP2 gene is associated with Danon disease. In summary, this variant is likely to be pathogenic, though additional studies are required to fully establish its cl inical significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at