rs727504600
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The ENST00000200639.9(LAMP2):c.121del(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 (★). 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
ENST00000200639.9 frameshift
ENST00000200639.9 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.70
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-120456712-CA-C is Pathogenic according to our data. Variant chrX-120456712-CA-C is described in ClinVar as [Pathogenic]. Clinvar id is 179062.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
LAMP2 | NM_002294.3 | c.121del | p.Cys41AlafsTer8 | frameshift_variant | 2/9 | ENST00000200639.9 | NP_002285.1 | |
LAMP2 | NM_001122606.1 | c.121del | p.Cys41AlafsTer8 | frameshift_variant | 2/9 | NP_001116078.1 | ||
LAMP2 | NM_013995.2 | c.121del | p.Cys41AlafsTer8 | frameshift_variant | 2/9 | NP_054701.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
LAMP2 | ENST00000200639.9 | c.121del | p.Cys41AlafsTer8 | frameshift_variant | 2/9 | 1 | NM_002294.3 | ENSP00000200639 | P3 | |
LAMP2 | ENST00000434600.6 | c.121del | p.Cys41AlafsTer8 | frameshift_variant | 2/9 | 1 | ENSP00000408411 | A1 | ||
LAMP2 | ENST00000371335.4 | c.121del | p.Cys41AlafsTer8 | frameshift_variant | 2/9 | 1 | ENSP00000360386 | A1 | ||
LAMP2 | ENST00000706600.1 | c.121del | p.Cys41AlafsTer8 | frameshift_variant | 2/9 | ENSP00000516464 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
Cov.:
22
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1080686Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0AN XY: 349648
GnomAD4 exome
Data not reliable, filtered out with message: AC0
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1080686
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24
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349648
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GnomAD4 genome Cov.: 22
GnomAD4 genome
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22
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Danon disease Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 09, 2013 | The Cys41fs variant in LAMP2 has not been reported in individuals with cardiomyo pathy or Danon disease or in large population studies. This frameshift variant i s predicted to alter the protein?s amino acid sequence beginning at position 41 and lead to a premature termination codon 8 amino acids downstream. This alterat ion is then predicted to lead to a truncated or absent protein. Loss of function of the LAMP2 gene is an established disease mechanism in males with Danon disea se. In summary, this variant meets our criteria to be classified as pathogenic ( http://pcpgm.partners.org/LMM) based upon the predicted impact to the protein. - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at