rs28937876
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_018965.4(TREM2):c.558G>T(p.Lys186Asn) variant causes a missense 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 Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
TREM2
NM_018965.4 missense
NM_018965.4 missense
Scores
1
2
9
Clinical Significance
Conservation
PhyloP100: 0.668
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TREM2 | NM_018965.4 | c.558G>T | p.Lys186Asn | missense_variant | 4/5 | ENST00000373113.8 | |
TREM2 | NM_001271821.2 | c.483-211G>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TREM2 | ENST00000373113.8 | c.558G>T | p.Lys186Asn | missense_variant | 4/5 | 1 | NM_018965.4 | P1 | |
TREM2 | ENST00000373122.8 | c.598G>T | p.Asp200Tyr | missense_variant | 4/5 | 1 | |||
TREM2 | ENST00000338469.3 | c.483-211G>T | intron_variant | 1 | |||||
ENST00000702590.1 | n.364+3428C>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 31
GnomAD4 exome
Cov.:
31
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Pathogenic:1Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 Pathogenic:1Uncertain:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Sep 01, 2002 | - - |
Uncertain significance, criteria provided, single submitter | curation | SIB Swiss Institute of Bioinformatics | Oct 17, 2019 | This variant is interpreted as a variant of uncertain significance for Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2 , autosomal recessive. The following ACMG Tag(s) were applied: PM2, PP3, PP1, PM3-Supporting. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MutationTaster
Benign
A;A;A
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
ClinPred
D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -8
Find out detailed SpliceAI scores and Pangolin per-transcript scores at