Variant 6-41198416-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_024807.4(TREML2):c.69C>G(p.Asp23Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,595,472 control chromosomes in the GnomAD database, including 13,039 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.092 ( 794 hom., cov: 33)

Exomes 𝑓: 0.12 ( 12245 hom. )

Consequence

TREML2
NM_024807.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.476

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015787482).

BP6

Variant 6-41198416-G-C is Benign according to our data. Variant chr6-41198416-G-C is described in ClinVar as [Benign]. Clinvar id is 769682.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.15 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TREML2	NM_024807.4 linkuse as main transcript	c.69C>G	p.Asp23Glu	missense_variant	2/5	ENST00000483722.2
TREML2	XM_011514917.3 linkuse as main transcript	c.55+2538C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TREML2	ENST00000483722.2 linkuse as main transcript	c.69C>G	p.Asp23Glu	missense_variant	2/5	1	NM_024807.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0917

AC:

13947

AN:

152100

Hom.:

793

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0254

Gnomad AMI

AF:

0.296

Gnomad AMR

AF:

0.0837

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.0831

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.0820

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.0866

GnomAD3 exomes

AF:

0.0587

AC:

13148

AN:

223886

Hom.:

981

AF XY:

0.0593

AC XY:

7104

AN XY:

119868

show subpopulations

Gnomad AFR exome

AF:

0.00996

Gnomad AMR exome

AF:

0.0472

Gnomad ASJ exome

AF:

0.0617

Gnomad EAS exome

AF:

0.0462

Gnomad SAS exome

AF:

0.0872

Gnomad FIN exome

AF:

0.0486

Gnomad NFE exome

AF:

0.0662

Gnomad OTH exome

AF:

0.0693

GnomAD4 exome

AF:

0.122

AC:

176617

AN:

1443252

Hom.:

12245

Cov.:

AF XY:

0.124

AC XY:

88684

AN XY:

718028

show subpopulations

Gnomad4 AFR exome

AF:

0.0176

Gnomad4 AMR exome

AF:

0.0936

Gnomad4 ASJ exome

AF:

0.135

Gnomad4 EAS exome

AF:

0.0876

Gnomad4 SAS exome

AF:

0.159

Gnomad4 FIN exome

AF:

0.0893

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.114

GnomAD4 genome

AF:

0.0917

AC:

13959

AN:

152220

Hom.:

794

Cov.:

AF XY:

0.0902

AC XY:

6713

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0253

Gnomad4 AMR

AF:

0.0835

Gnomad4 ASJ

AF:

0.127

Gnomad4 EAS

AF:

0.0830

Gnomad4 SAS

AF:

0.159

Gnomad4 FIN

AF:

0.0820

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.0923

Alfa

AF:

0.103

Hom.:

247

Bravo

AF:

0.0888

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.103

AC:

12561

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 05, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.88

Cadd

Benign

0.18

Dann

Benign

0.14

DEOGEN2

Benign

0.0011

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0011

LIST_S2

Benign

0.30

MetaRNN

Benign

0.0016

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.9

MutationTaster

Benign

1.0

PrimateAI

Benign

0.32

PROVEAN

Benign

1.4

REVEL

Benign

0.11

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.012

MutPred

0.36

Gain of sheet (P = 0.0344);

MPC

0.20

ClinPred

0.0086

GERP RS

3.7

Varity_R

0.027

gMVP

0.13

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

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