chr6-41158663-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000338469.3(TREM2):c.600G>C(p.Trp200Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,458,044 control chromosomes in the GnomAD database, with no homozygous occurrence. 9/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
TREM2
ENST00000338469.3 missense
ENST00000338469.3 missense
Scores
1
10
Clinical Significance
Conservation
PhyloP100: 0.406
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TREM2 | NM_018965.4 | c.*101G>C | 3_prime_UTR_variant | 5/5 | ENST00000373113.8 | ||
TREM2 | NM_001271821.2 | c.600G>C | p.Trp200Cys | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TREM2 | ENST00000338469.3 | c.600G>C | p.Trp200Cys | missense_variant | 4/4 | 1 | |||
TREM2 | ENST00000373113.8 | c.*101G>C | 3_prime_UTR_variant | 5/5 | 1 | NM_018965.4 | P1 | ||
TREM2 | ENST00000373122.8 | c.*165G>C | 3_prime_UTR_variant | 5/5 | 1 | ||||
ENST00000702590.1 | n.364+3100C>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.00000411 AC: 1AN: 243500Hom.: 0 AF XY: 0.00000761 AC XY: 1AN XY: 131444
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1458044Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2AN XY: 724878
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GnomAD4 genome ? Cov.: 32
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Cov.:
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 17, 2023 | This variant has not been reported in the literature in individuals affected with TREM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2135653). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant is present in population databases (no rsID available, gnomAD 0.006%). The TREM2 gene has multiple clinically relevant transcripts. This variant occurs in alternate transcript NM_001271821.1, and corresponds to NM_018965.3:c.*101G>C in the primary transcript. This variant occurs in a non-coding region of the TREM2 gene. It does not change the encoded amino acid sequence of the TREM2 protein. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N
Polyphen
D
Vest4
MutPred
Loss of catalytic residue at L198 (P = 0.0064);
MVP
ClinPred
T
GERP RS
Splicing
Name
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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