Variant 6-41194427-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000483722.2(TREML2):c.783C>G(p.Ile261Met) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000213 in 1,408,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TREML2
ENST00000483722.2 missense, splice_region

Scores

Splicing: ADA: 0.003026

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.23

Variant links:

Genes affected

TREML2 (HGNC:21092): (triggering receptor expressed on myeloid cells like 2) TREML2 is located in a gene cluster on chromosome 6 with the single Ig variable (IgV) domain activating receptors TREM1 (MIM 605085) and TREM2 (MIM 605086), but it has distinct structural and functional properties (Allcock et al., 2003 [PubMed 12645956]).[supplied by OMIM, Mar 2008]

TREML2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12501869).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREML2	NM_024807.4 linkuse as main transcript	c.783C>G	p.Ile261Met	missense_variant, splice_region_variant	3/5	ENST00000483722.2	NP_079083.2
TREML2	XM_011514917.3 linkuse as main transcript	c.462C>G	p.Ile154Met	missense_variant, splice_region_variant	2/4		XP_011513219.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TREML2	ENST00000483722.2 linkuse as main transcript	c.783C>G	p.Ile261Met	missense_variant, splice_region_variant	3/5	1	NM_024807.4	ENSP00000418767	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000578

AC:

AN:

172922

Hom.:

AF XY:

0.00

AC XY:

AN XY:

91428

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000783

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000213

AC:

AN:

1408198

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

695064

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000272

Gnomad4 SAS exome

AF:

0.0000125

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000171

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 30, 2024

The c.783C>G (p.I261M) alteration is located in exon 3 (coding exon 3) of the TREML2 gene. This alteration results from a C to G substitution at nucleotide position 783, causing the isoleucine (I) at amino acid position 261 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.55

DEOGEN2

Benign

0.018

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.32

M_CAP

Benign

0.0038

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.87

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.48

REVEL

Benign

0.12

Sift

Uncertain

0.021

Sift4G

Benign

0.32

Polyphen

0.0040

Vest4

0.20

MutPred

0.26

Gain of disorder (P = 0.0332);

MVP

0.22

MPC

0.22

ClinPred

0.16

GERP RS

4.3

Varity_R

0.14

gMVP

0.070

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0030

dbscSNV1_RF

Benign

0.17

SpliceAI score (max)

0.050

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over