Variant 6-41194441-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024807.4(TREML2):c.769T>C(p.Ser257Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000028 in 1,426,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

TREML2
NM_024807.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0780

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043006063).

BP6

Variant 6-41194441-A-G is Benign according to our data. Variant chr6-41194441-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2396137.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TREML2	NM_024807.4 linkuse as main transcript	c.769T>C	p.Ser257Pro	missense_variant	3/5	ENST00000483722.2	NP_079083.2	Q5T2D2
TREML2	XM_011514917.3 linkuse as main transcript	c.448T>C	p.Ser150Pro	missense_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.769T>C	p.Ser257Pro	missense_variant	3/5	1	NM_024807.4	ENSP00000418767.1		Q5T2D2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000280

AC:

AN:

1426882

Hom.:

Cov.:

AF XY:

0.00000425

AC XY:

AN XY:

706324

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000366

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.87

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.0013

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.0057

LIST_S2

Benign

0.30

M_CAP

Benign

0.0039

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.81

PrimateAI

Benign

0.27

PROVEAN

Benign

0.48

REVEL

Benign

0.043

Sift

Benign

0.27

Sift4G

Benign

0.30

Polyphen

0.0

Vest4

0.031

MutPred

0.31

Gain of catalytic residue at P256 (P = 0.012);

MVP

0.14

MPC

0.26

ClinPred

0.19

GERP RS

1.1

Varity_R

0.068

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over