rs730880344
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_002294.3(LAMP2):c.129_130insAT(p.Ala44MetfsTer6) 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 (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 22)
Consequence
LAMP2
NM_002294.3 frameshift
NM_002294.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.38
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 Pathogenic. Variant got 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-120456704-C-CAT is Pathogenic according to our data. Variant chrX-120456704-C-CAT is described in ClinVar as [Likely_pathogenic]. Clinvar id is 177994.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.129_130insAT | p.Ala44MetfsTer6 | frameshift_variant | 2/9 | ENST00000200639.9 | |
LAMP2 | NM_001122606.1 | c.129_130insAT | p.Ala44MetfsTer6 | frameshift_variant | 2/9 | ||
LAMP2 | NM_013995.2 | c.129_130insAT | p.Ala44MetfsTer6 | frameshift_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
LAMP2 | ENST00000200639.9 | c.129_130insAT | p.Ala44MetfsTer6 | frameshift_variant | 2/9 | 1 | NM_002294.3 | P3 | |
LAMP2 | ENST00000371335.4 | c.129_130insAT | p.Ala44MetfsTer6 | frameshift_variant | 2/9 | 1 | A1 | ||
LAMP2 | ENST00000434600.6 | c.129_130insAT | p.Ala44MetfsTer6 | frameshift_variant | 2/9 | 1 | A1 | ||
LAMP2 | ENST00000706600.1 | c.129_130insAT | p.Ala44MetfsTer6 | frameshift_variant | 2/9 |
Frequencies
GnomAD3 genomes ? Cov.: 22
GnomAD3 genomes
?
Cov.:
22
GnomAD4 exome Cov.: 24
GnomAD4 exome
Cov.:
24
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
Hypertrophic cardiomyopathy;C0878677:Danon disease Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 23, 2012 | The Ala44fs variant in LAMP2 has not been previously reported in the literature or identified by our laboratory. The Ala44fs variant in LAMP2 is predicted to ca use a frameshift, which alters the protein's amino acid sequence beginning at co don 44 and leads to a premature stop codon six amino acids downstream. This alt eration is then predicted to lead to a truncated or absent protein. Loss of fun ction is an established mechanism of disease for the LAMP2 gene, which makes it highly likely that the Ala44fs variant is pathogenic. Pathogenic variants in LAM P2 have been associated with Danon disease. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at