rs146348065

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001127208.3(TET2):c.5167C>T(p.Pro1723Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0106 in 1,551,848 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0066 ( 5 hom., cov: 32)

Exomes 𝑓: 0.011 ( 108 hom. )

Consequence

TET2
NM_001127208.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.127

Publications

38 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=0.00503546).

BP6

Variant 4-105275677-C-T is Benign according to our data. Variant chr4-105275677-C-T is described in ClinVar as Benign. ClinVar VariationId is 135292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0066 (1005/152272) while in subpopulation NFE AF = 0.0109 (743/68010). AF 95% confidence interval is 0.0103. There are 5 homozygotes in GnomAd4. There are 442 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TET2	NM_001127208.3 link	c.5167C>T	p.Pro1723Ser	missense_variant	Exon 11 of 11	ENST00000380013.9	NP_001120680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9 link	c.5167C>T	p.Pro1723Ser	missense_variant	Exon 11 of 11	5	NM_001127208.3	ENSP00000369351.4

Frequencies

GnomAD3 genomes

AF:

0.00660

AC:

1004

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00232

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00635

Gnomad ASJ

AF:

0.00547

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.0109

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00727

AC:

1144

AN:

157324

AF XY:

0.00714

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.00640

Gnomad ASJ exome

AF:

0.00670

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00202

Gnomad NFE exome

AF:

0.0130

Gnomad OTH exome

AF:

0.00948

GnomAD4 exome

AF:

0.0110

AC:

15428

AN:

1399576

Hom.:

108

Cov.:

AF XY:

0.0107

AC XY:

7358

AN XY:

690272

show subpopulations

African (AFR)

AF:

0.00199

AC:

AN:

31598

American (AMR)

AF:

0.00664

AC:

237

AN:

35706

Ashkenazi Jewish (ASJ)

AF:

0.00592

AC:

149

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35740

South Asian (SAS)

AF:

0.00230

AC:

182

AN:

79236

European-Finnish (FIN)

AF:

0.00201

AC:

AN:

49360

Middle Eastern (MID)

AF:

0.00825

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.0131

AC:

14127

AN:

1078976

Other (OTH)

AF:

0.00902

AC:

524

AN:

58078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

905

1811

2716

3622

4527

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

550

1100

1650

2200

2750

<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:

0.00660

AC:

1005

AN:

152272

Hom.:

Cov.:

AF XY:

0.00594

AC XY:

442

AN XY:

74444

show subpopulations

African (AFR)

AF:

0.00231

AC:

AN:

41550

American (AMR)

AF:

0.00634

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00547

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00311

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00160

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0109

AC:

743

AN:

68010

Other (OTH)

AF:

0.00662

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

105

158

210

263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00945

Hom.:

Bravo

AF:

0.00700

TwinsUK

AF:

0.0127

AC:

ALSPAC

AF:

0.0143

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.0123

AC:

ExAC

AF:

0.00532

AC:

136

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TET2: BP4, BS1, BS2 -

not specified

Benign:1Other:1

Apr 28, 2021

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

0.063

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.89

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.013

T;T;T

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.71

T;T;.

MetaRNN

Benign

0.0050

T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.7

.;L;L

PhyloP100

-0.13

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.8

D;D;D

REVEL

Benign

0.034

Sift

Benign

0.25

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.13

B;B;B

Vest4

0.049

MVP

0.26

MPC

0.089

ClinPred

0.0081

GERP RS

1.3

Varity_R

0.049

gMVP

0.54

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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