rs386834142

chr6-41163036-ATCC-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP5

The NM_018965.4(TREM2):c.40+4_40+6del variant causes a splice donor 5th base, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TREM2 NM_018965.4 splice_donor_5th_base, intron
• Clinical Significance: Pathogenic/Likely pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 1.16

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PP5: Variant 6-41163036-ATCC-A is Pathogenic according to our data. Variant chr6-41163036-ATCC-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 56723.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-41163036-ATCC-A is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TREM2	NM_018965.4	c.40+4_40+6del		splice_donor_5th_base_variant, intron_variant		ENST00000373113.8
TREM2	NM_001271821.2	c.40+4_40+6del		splice_donor_5th_base_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TREM2	ENST00000373113.8	c.40+4_40+6del		splice_donor_5th_base_variant, intron_variant		1	NM_018965.4	P1
TREM2	ENST00000338469.3	c.40+4_40+6del		splice_donor_5th_base_variant, intron_variant		1
TREM2	ENST00000373122.8	c.40+4_40+6del		splice_donor_5th_base_variant, intron_variant		1
	ENST00000702590.1	n.364+7475_364+7477del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic/Likely pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	GeneReviews	Mar 12, 2015	- -
Likely pathogenic, no assertion criteria provided	literature only	Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	-	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs386834142; hg19: chr6-41130774;