Variant chr4-105235030-C-T 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_001127208.3(TET2):c.1088C>T(p.Pro363Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0529 in 1,614,090 control chromosomes in the GnomAD database, including 2,635 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.044 ( 213 hom., cov: 32)

Exomes 𝑓: 0.054 ( 2422 hom. )

Consequence

TET2
NM_001127208.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 1.78

Variant links:

Genes affected

TET2 (HGNC:25941): (tet methylcytosine dioxygenase 2) The protein encoded by this gene is a methylcytosine dioxygenase that catalyzes the conversion of methylcytosine to 5-hydroxymethylcytosine. The encoded protein is involved in myelopoiesis, and defects in this gene have been associated with several myeloproliferative disorders. Two variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

TET2 links:

TET2 (HGNC:):

TET2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0015110075).

BP6

Variant 4-105235030-C-T is Benign according to our data. Variant chr4-105235030-C-T is described in ClinVar as [Benign]. Clinvar id is 135309.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TET2	NM_001127208.3 linkuse as main transcript	c.1088C>T	p.Pro363Leu	missense_variant	3/11	ENST00000380013.9	NP_001120680.1	Q6N021-1A0A158SIU0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9 linkuse as main transcript	c.1088C>T	p.Pro363Leu	missense_variant	3/11	5	NM_001127208.3	ENSP00000369351.4		Q6N021-1

Frequencies

GnomAD3 genomes

AF:

0.0444

AC:

6761

AN:

152160

Hom.:

213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00871

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.0294

Gnomad ASJ

AF:

0.0559

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0488

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0598

Gnomad OTH

AF:

0.0473

GnomAD3 exomes

AF:

0.0497

AC:

12483

AN:

250942

Hom.:

418

AF XY:

0.0533

AC XY:

7235

AN XY:

135614

show subpopulations

Gnomad AFR exome

AF:

0.00831

Gnomad AMR exome

AF:

0.0217

Gnomad ASJ exome

AF:

0.0560

Gnomad EAS exome

AF:

0.000327

Gnomad SAS exome

AF:

0.0575

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.0577

Gnomad OTH exome

AF:

0.0533

GnomAD4 exome

AF:

0.0538

AC:

78599

AN:

1461812

Hom.:

2422

Cov.:

AF XY:

0.0550

AC XY:

39979

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00818

Gnomad4 AMR exome

AF:

0.0235

Gnomad4 ASJ exome

AF:

0.0554

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0589

Gnomad4 FIN exome

AF:

0.107

Gnomad4 NFE exome

AF:

0.0553

Gnomad4 OTH exome

AF:

0.0526

GnomAD4 genome

AF:

0.0444

AC:

6757

AN:

152278

Hom.:

213

Cov.:

AF XY:

0.0472

AC XY:

3516

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.00869

Gnomad4 AMR

AF:

0.0294

Gnomad4 ASJ

AF:

0.0559

Gnomad4 EAS

AF:

0.000964

Gnomad4 SAS

AF:

0.0486

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.0598

Gnomad4 OTH

AF:

0.0473

Alfa

AF:

0.0545

Hom.:

524

Bravo

AF:

0.0362

TwinsUK

AF:

0.0510

AC:

189

ALSPAC

AF:

0.0545

AC:

210

ESP6500AA

AF:

0.0102

AC:

ESP6500EA

AF:

0.0590

AC:

507

ExAC

AF:

0.0482

AC:

5849

Asia WGS

AF:

0.0210

AC:

AN:

3478

EpiCase

AF:

0.0593

EpiControl

AF:

0.0572

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

.;T;T;T;.

Eigen

Benign

0.052

Eigen_PC

Benign

0.18

FATHMM_MKL

Benign

0.70

LIST_S2

Uncertain

0.90

D;D;D;.;D

MetaRNN

Benign

0.0015

T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.3

M;.;M;M;.

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.7

N;N;N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0070

D;D;D;D;D

Sift4G

Uncertain

0.023

D;T;T;T;D

Polyphen

0.57

P;B;B;B;.

Vest4

0.16

MPC

0.096

ClinPred

0.0076

GERP RS

5.0

Varity_R

0.18

gMVP

0.14

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