4-105234028-C-G

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.86C>G(p.Pro29Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0319 in 1,613,852 control chromosomes in the GnomAD database, including 2,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P29S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.040 ( 281 hom., cov: 33)

Exomes 𝑓: 0.031 ( 2109 hom. )

Consequence

TET2
NM_001127208.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: 0.849

Publications

54 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=0.0011830032).

BP6

Variant 4-105234028-C-G is Benign according to our data. Variant chr4-105234028-C-G is described in ClinVar as Benign. ClinVar VariationId is 135316.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TET2	NM_001127208.3 link	c.86C>G	p.Pro29Arg	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.86C>G	p.Pro29Arg	missense_variant	Exon 3 of 11	5	NM_001127208.3	ENSP00000369351.4		Q6N021-1

Frequencies

GnomAD3 genomes

AF:

0.0398

AC:

6048

AN:

152142

Hom.:

278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0299

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0723

Gnomad ASJ

AF:

0.0308

Gnomad EAS

AF:

0.196

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0691

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0170

Gnomad OTH

AF:

0.0435

GnomAD2 exomes

AF:

0.0629

AC:

15788

AN:

250816

AF XY:

0.0625

show subpopulations

Gnomad AFR exome

AF:

0.0315

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.0335

Gnomad EAS exome

AF:

0.205

Gnomad FIN exome

AF:

0.0667

Gnomad NFE exome

AF:

0.0181

Gnomad OTH exome

AF:

0.0507

GnomAD4 exome

AF:

0.0311

AC:

45469

AN:

1461592

Hom.:

2109

Cov.:

AF XY:

0.0335

AC XY:

24384

AN XY:

727092

show subpopulations

African (AFR)

AF:

0.0329

AC:

1100

AN:

33474

American (AMR)

AF:

0.109

AC:

4873

AN:

44650

Ashkenazi Jewish (ASJ)

AF:

0.0362

AC:

947

AN:

26132

East Asian (EAS)

AF:

0.203

AC:

8048

AN:

39658

South Asian (SAS)

AF:

0.117

AC:

10098

AN:

86204

European-Finnish (FIN)

AF:

0.0657

AC:

3510

AN:

53406

Middle Eastern (MID)

AF:

0.0728

AC:

420

AN:

5766

European-Non Finnish (NFE)

AF:

0.0126

AC:

14029

AN:

1111922

Other (OTH)

AF:

0.0405

AC:

2444

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

2301

4602

6903

9204

11505

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

726

1452

2178

2904

3630

<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:

0.0398

AC:

6057

AN:

152260

Hom.:

281

Cov.:

AF XY:

0.0448

AC XY:

3334

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0299

AC:

1243

AN:

41554

American (AMR)

AF:

0.0730

AC:

1115

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0308

AC:

107

AN:

3472

East Asian (EAS)

AF:

0.196

AC:

1014

AN:

5168

South Asian (SAS)

AF:

0.121

AC:

583

AN:

4830

European-Finnish (FIN)

AF:

0.0691

AC:

733

AN:

10612

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0170

AC:

1157

AN:

68020

Other (OTH)

AF:

0.0430

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

284

569

853

1138

1422

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

222

296

370

<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:

0.0249

Hom.:

Bravo

AF:

0.0416

TwinsUK

AF:

0.0140

AC:

ALSPAC

AF:

0.0119

AC:

ESP6500AA

AF:

0.0300

AC:

132

ESP6500EA

AF:

0.0155

AC:

133

ExAC

AF:

0.0605

AC:

7343

Asia WGS

AF:

0.137

AC:

475

AN:

3478

EpiCase

AF:

0.0215

EpiControl

AF:

0.0197

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 05, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

- -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 22. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.068

.;T;T;T;.;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.59

T;T;T;.;T;T

MetaRNN

Benign

0.0012

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.;M;M;.;.

PhyloP100

0.85

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.1

D;D;D;D;D;D

REVEL

Benign

0.084

Sift

Uncertain

0.0030

D;D;D;D;D;T

Sift4G

Benign

0.17

T;T;T;T;T;D

Polyphen

0.99

D;P;P;P;.;.

Vest4

0.47

MPC

0.27

ClinPred

0.033

GERP RS

4.5

Varity_R

0.23

gMVP

0.24

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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