NM_001127208.3:c.652G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001127208.3(TET2):c.652G>A(p.Val218Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 1,613,946 control chromosomes in the GnomAD database, including 4,268 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.10 ( 1907 hom., cov: 33)

Exomes 𝑓: 0.032 ( 2361 hom. )

Consequence

TET2
NM_001127208.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: 0.755

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022783577).

BP6

Variant 4-105234594-G-A is Benign according to our data. Variant chr4-105234594-G-A is described in ClinVar as [Benign]. Clinvar id is 135321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TET2	NM_001127208.3 link	c.652G>A	p.Val218Met	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.652G>A	p.Val218Met	missense_variant	Exon 3 of 11	5	NM_001127208.3	ENSP00000369351.4		Q6N021-1

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

15865

AN:

152066

Hom.:

1899

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.0264

Gnomad AMR

AF:

0.0475

Gnomad ASJ

AF:

0.0544

Gnomad EAS

AF:

0.0665

Gnomad SAS

AF:

0.0422

Gnomad FIN

AF:

0.0663

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0212

Gnomad OTH

AF:

0.0891

GnomAD3 exomes

AF:

0.0511

AC:

12812

AN:

250900

Hom.:

926

AF XY:

0.0466

AC XY:

6317

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.0213

Gnomad ASJ exome

AF:

0.0501

Gnomad EAS exome

AF:

0.0737

Gnomad SAS exome

AF:

0.0382

Gnomad FIN exome

AF:

0.0693

Gnomad NFE exome

AF:

0.0225

Gnomad OTH exome

AF:

0.0393

GnomAD4 exome

AF:

0.0322

AC:

47041

AN:

1461762

Hom.:

2361

Cov.:

AF XY:

0.0317

AC XY:

23052

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.304

Gnomad4 AMR exome

AF:

0.0245

Gnomad4 ASJ exome

AF:

0.0504

Gnomad4 EAS exome

AF:

0.0782

Gnomad4 SAS exome

AF:

0.0376

Gnomad4 FIN exome

AF:

0.0638

Gnomad4 NFE exome

AF:

0.0192

Gnomad4 OTH exome

AF:

0.0502

GnomAD4 genome

AF:

0.105

AC:

15914

AN:

152184

Hom.:

1907

Cov.:

AF XY:

0.105

AC XY:

7790

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.291

Gnomad4 AMR

AF:

0.0474

Gnomad4 ASJ

AF:

0.0544

Gnomad4 EAS

AF:

0.0665

Gnomad4 SAS

AF:

0.0421

Gnomad4 FIN

AF:

0.0663

Gnomad4 NFE

AF:

0.0212

Gnomad4 OTH

AF:

0.0882

Alfa

AF:

0.0337

Hom.:

764

Bravo

AF:

0.111

TwinsUK

AF:

0.0181

AC:

ALSPAC

AF:

0.0228

AC:

ESP6500AA

AF:

0.284

AC:

1253

ESP6500EA

AF:

0.0209

AC:

180

ExAC

AF:

0.0548

AC:

6656

EpiCase

AF:

0.0206

EpiControl

AF:

0.0223

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Aug 11, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

In silico analysis supports that this missense variant does not alter protein structure/function -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 10, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

0.055

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.5

DANN

Benign

0.84

DEOGEN2

Benign

0.0054

.;T;T;T;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.24

T;T;T;.;T

MetaRNN

Benign

0.0023

T;T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-2.0

N;.;N;N;.

PrimateAI

Benign

0.29

PROVEAN

Benign

0.93

N;N;N;N;N

REVEL

Benign

0.051

Sift

Benign

1.0

T;T;T;T;T

Sift4G

Benign

0.14

T;T;T;T;T

Polyphen

0.0020

B;B;B;B;.

Vest4

0.091

MPC

0.070

ClinPred

0.00029

GERP RS

2.4

Varity_R

0.021

gMVP

0.16

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