rs386834141
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_018965.4(TREM2):c.313del(p.Ala105ArgfsTer84) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. A105A) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_018965.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TREM2 | NM_018965.4 | c.313del | p.Ala105ArgfsTer84 | frameshift_variant | 2/5 | ENST00000373113.8 | |
TREM2 | NM_001271821.2 | c.313del | p.Ala105ArgfsTer62 | frameshift_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TREM2 | ENST00000373113.8 | c.313del | p.Ala105ArgfsTer84 | frameshift_variant | 2/5 | 1 | NM_018965.4 | P1 | |
TREM2 | ENST00000373122.8 | c.313del | p.Ala105ArgfsTer140 | frameshift_variant | 2/5 | 1 | |||
TREM2 | ENST00000338469.3 | c.313del | p.Ala105ArgfsTer62 | frameshift_variant | 2/4 | 1 | |||
ENST00000702590.1 | n.364+5778del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251464Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135904
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461886Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727244
GnomAD4 genome Cov.: 32
ClinVar
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) | - | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2022 | TREM2: PVS1, PM2, PM3 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at