chr6-41158711-T-A

Variant names:

• chr6-41158711-T-A
• ENST00000338469.3:c.552A>T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001271821.2(TREM2):​c.552A>T​(p.Pro184Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TREM2 NM_001271821.2 synonymous
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0250

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]

ENSG00000290034 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-0.025 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TREM2	NM_018965.4	c.*53A>T		3_prime_UTR_variant	Exon 5 of 5	ENST00000373113.8	NP_061838.1
TREM2	NM_001271821.2	c.552A>T	p.Pro184Pro	synonymous_variant	Exon 4 of 4		NP_001258750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TREM2	ENST00000338469.3	c.552A>T	p.Pro184Pro	synonymous_variant	Exon 4 of 4	1		ENSP00000342651.4
TREM2	ENST00000373113	c.*53A>T		3_prime_UTR_variant	Exon 5 of 5	1	NM_018965.4	ENSP00000362205.3
TREM2	ENST00000373122	c.*117A>T		3_prime_UTR_variant	Exon 5 of 5	1		ENSP00000362214.4
ENSG00000290034	ENST00000702590.1	n.364+3148T>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Mar 11, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant has not been reported in the literature in individuals affected with TREM2-related conditions. 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. This variant is not present in population databases (gnomAD no frequency). 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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.79

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-41126449;