NM_001127208.3:c.1088C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: 1.78

Publications

43 publications found

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-AS1 (HGNC:41125): (TET2 antisense RNA 1)

TET2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 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 VariationId is 135309.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
TET2	NM_001127208.3 link	c.1088C>T	p.Pro363Leu	missense_variant	Exon 3 of 11	ENST00000380013.9	NP_001120680.1	Q6N021-1A0A158SIU0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9 link	c.1088C>T	p.Pro363Leu	missense_variant	Exon 3 of 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

GnomAD2 exomes

AF:

0.0497

AC:

12483

AN:

250942

AF XY:

0.0533

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 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

African (AFR)

AF:

0.00818

AC:

274

AN:

33478

American (AMR)

AF:

0.0235

AC:

1051

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0554

AC:

1448

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39680

South Asian (SAS)

AF:

0.0589

AC:

5082

AN:

86250

European-Finnish (FIN)

AF:

0.107

AC:

5702

AN:

53414

Middle Eastern (MID)

AF:

0.0621

AC:

358

AN:

5766

European-Non Finnish (NFE)

AF:

0.0553

AC:

61503

AN:

1111978

Other (OTH)

AF:

0.0526

AC:

3179

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

4550

9100

13650

18200

22750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2234

4468

6702

8936

11170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0444

AC:

6757

AN:

152278

Hom.:

213

Cov.:

AF XY:

0.0472

AC XY:

3516

AN XY:

74432

show subpopulations

African (AFR)

AF:

0.00869

AC:

361

AN:

41560

American (AMR)

AF:

0.0294

AC:

450

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0559

AC:

194

AN:

3470

East Asian (EAS)

AF:

0.000964

AC:

AN:

5186

South Asian (SAS)

AF:

0.0486

AC:

234

AN:

4816

European-Finnish (FIN)

AF:

0.114

AC:

1212

AN:

10592

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0598

AC:

4067

AN:

68030

Other (OTH)

AF:

0.0473

AC:

100

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

320

641

961

1282

1602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

264

352

440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0513

Hom.:

699

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:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 01, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

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

(source)

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;.

PhyloP100

1.8

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

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over