Variant chr19-3000657-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003260.5(TLE2):c.2114G>A(p.Ser705Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0049 in 1,587,666 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0084 ( 6 hom., cov: 30)

Exomes 𝑓: 0.0045 ( 39 hom. )

Consequence

TLE2
NM_003260.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 7.84

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009703219).

BP6

Variant 19-3000657-C-T is Benign according to our data. Variant chr19-3000657-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1679860.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00453 (6507/1435534) while in subpopulation MID AF= 0.0346 (195/5642). AF 95% confidence interval is 0.0306. There are 39 homozygotes in gnomad4_exome. There are 3226 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TLE2	NM_003260.5 linkuse as main transcript	c.2114G>A	p.Ser705Asn	missense_variant	19/20	ENST00000262953.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TLE2	ENST00000262953.11 linkuse as main transcript	c.2114G>A	p.Ser705Asn	missense_variant	19/20	1	NM_003260.5	A1	Q04725-1

Frequencies

GnomAD3 genomes

AF:

0.00835

AC:

1270

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0149

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00985

Gnomad ASJ

AF:

0.00749

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00249

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.0382

Gnomad NFE

AF:

0.00454

Gnomad OTH

AF:

0.0149

GnomAD3 exomes

AF:

0.00553

AC:

1156

AN:

208862

Hom.:

AF XY:

0.00517

AC XY:

583

AN XY:

112764

show subpopulations

Gnomad AFR exome

AF:

0.0128

Gnomad AMR exome

AF:

0.00697

Gnomad ASJ exome

AF:

0.00776

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00972

Gnomad NFE exome

AF:

0.00492

Gnomad OTH exome

AF:

0.00845

GnomAD4 exome

AF:

0.00453

AC:

6507

AN:

1435534

Hom.:

Cov.:

AF XY:

0.00453

AC XY:

3226

AN XY:

711546

show subpopulations

Gnomad4 AFR exome

AF:

0.0140

Gnomad4 AMR exome

AF:

0.00724

Gnomad4 ASJ exome

AF:

0.00710

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00224

Gnomad4 FIN exome

AF:

0.00932

Gnomad4 NFE exome

AF:

0.00387

Gnomad4 OTH exome

AF:

0.00768

GnomAD4 genome

AF:

0.00836

AC:

1272

AN:

152132

Hom.:

Cov.:

AF XY:

0.00832

AC XY:

619

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.0149

Gnomad4 AMR

AF:

0.00983

Gnomad4 ASJ

AF:

0.00749

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.0107

Gnomad4 NFE

AF:

0.00453

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00543

Hom.:

Bravo

AF:

0.00860

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.0127

AC:

ESP6500EA

AF:

0.00399

AC:

ExAC

AF:

0.00509

AC:

613

Asia WGS

AF:

0.00375

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

Pathogenic

0.57

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.54

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.43

T;.;.;.

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;.;D

MetaRNN

Benign

0.0097

T;T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.7

L;.;.;.

MutationTaster

Benign

0.99

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

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-2.6

D;D;D;.

REVEL

Benign

0.20

Sift

Uncertain

0.025

D;D;D;.

Sift4G

Uncertain

0.046

D;D;D;D

Polyphen

0.97

D;.;.;.

Vest4

0.75

MVP

0.73

MPC

0.92

ClinPred

0.023

GERP RS

4.0

Varity_R

0.58

gMVP

0.60

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