rs386834140
Positions:
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_018965.4(TREM2):c.269del(p.Gly90ValfsTer99) 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 (no stars). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Consequence
TREM2
NM_018965.4 frameshift
NM_018965.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.653
Genes affected
TREM2 (HGNC:17761): (triggering receptor expressed on myeloid cells 2) This gene encodes a membrane protein that forms a receptor signaling complex with the TYRO protein tyrosine kinase binding protein. The encoded protein functions in immune response and may be involved in chronic inflammation by triggering the production of constitutive inflammatory cytokines. Defects in this gene are a cause of polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Nov 2012]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 11 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 6-41161384-AC-A is Pathogenic according to our data. Variant chr6-41161384-AC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 56721.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-41161384-AC-A is described in Lovd as [Pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TREM2 | NM_018965.4 | c.269del | p.Gly90ValfsTer99 | frameshift_variant | 2/5 | ENST00000373113.8 | |
TREM2 | NM_001271821.2 | c.269del | p.Gly90ValfsTer77 | frameshift_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TREM2 | ENST00000373113.8 | c.269del | p.Gly90ValfsTer99 | frameshift_variant | 2/5 | 1 | NM_018965.4 | P1 | |
TREM2 | ENST00000373122.8 | c.269del | p.Gly90ValfsTer155 | frameshift_variant | 2/5 | 1 | |||
TREM2 | ENST00000338469.3 | c.269del | p.Gly90ValfsTer77 | frameshift_variant | 2/4 | 1 | |||
ENST00000702590.1 | n.364+5824del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 Pathogenic:1
Likely pathogenic, no assertion criteria provided | literature only | Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) | - | - - |
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