Variant 19-3011088-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_003260.5(TLE2):c.946G>A(p.Gly316Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0102 in 1,610,450 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0064 ( 5 hom., cov: 31)

Exomes 𝑓: 0.011 ( 94 hom. )

Consequence

TLE2
NM_003260.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 4.62

Variant links:

Genes affected

TLE2 (HGNC:11838): (TLE family member 2, transcriptional corepressor) Enables transcription corepressor activity. Involved in negative regulation of canonical Wnt signaling pathway and negative regulation of transcription, DNA-templated. Located in focal adhesion and nuclear body. [provided by Alliance of Genome Resources, Apr 2022]

TLE2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01025629).

BP6

Variant 19-3011088-C-T is Benign according to our data. Variant chr19-3011088-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1679861.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLE2	NM_003260.5 linkuse as main transcript	c.946G>A	p.Gly316Arg	missense_variant	12/20	ENST00000262953.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLE2	ENST00000262953.11 linkuse as main transcript	c.946G>A	p.Gly316Arg	missense_variant	12/20	1	NM_003260.5	A1	Q04725-1

Frequencies

GnomAD3 genomes

AF:

0.00641

AC:

975

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00446

Gnomad ASJ

AF:

0.0115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0107

Gnomad OTH

AF:

0.00574

GnomAD3 exomes

AF:

0.00711

AC:

1722

AN:

242080

Hom.:

AF XY:

0.00733

AC XY:

968

AN XY:

132008

show subpopulations

Gnomad AFR exome

AF:

0.00190

Gnomad AMR exome

AF:

0.00257

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00240

Gnomad FIN exome

AF:

0.00329

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.00749

GnomAD4 exome

AF:

0.0106

AC:

15511

AN:

1458254

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

7600

AN XY:

725274

show subpopulations

Gnomad4 AFR exome

AF:

0.00165

Gnomad4 AMR exome

AF:

0.00289

Gnomad4 ASJ exome

AF:

0.0119

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00245

Gnomad4 FIN exome

AF:

0.00376

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.00806

GnomAD4 genome

AF:

0.00641

AC:

976

AN:

152196

Hom.:

Cov.:

AF XY:

0.00579

AC XY:

431

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00217

Gnomad4 AMR

AF:

0.00445

Gnomad4 ASJ

AF:

0.0115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00283

Gnomad4 NFE

AF:

0.0107

Gnomad4 OTH

AF:

0.00568

Alfa

AF:

0.0108

Hom.:

Bravo

AF:

0.00729

TwinsUK

AF:

0.0132

AC:

ALSPAC

AF:

0.0101

AC:

ESP6500AA

AF:

0.00122

AC:

ESP6500EA

AF:

0.0124

AC:

104

ExAC

AF:

0.00711

AC:

859

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lymphopenia;C0853697:Neutropenia

Benign:1

Likely benign, no assertion criteria provided

research

Department of Biosciences, University of Milan

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.10

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.56

D;.;.;.;.;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.96

D;D;D;.;.;D

MetaRNN

Benign

0.010

T;T;T;T;T;T

MetaSVM

Uncertain

-0.21

MutationAssessor

Pathogenic

3.1

M;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-5.7

D;D;D;.;D;.

REVEL

Uncertain

0.35

Sift

Uncertain

0.0010

D;D;D;.;D;.

Sift4G

Uncertain

0.016

D;D;D;D;D;D

Polyphen

1.0

D;.;.;.;.;.

Vest4

0.75

MutPred

0.45

Gain of sheet (P = 4e-04);.;.;.;.;.;

MVP

0.80

MPC

0.47

ClinPred

0.029

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.64

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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