rs142312318

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.5152G>T(p.Val1718Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00651 in 1,551,956 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0043 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0068 ( 31 hom. )

Consequence

TET2
NM_001127208.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: -0.0290

Publications

26 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=0.0058729947).

BP6

Variant 4-105275662-G-T is Benign according to our data. Variant chr4-105275662-G-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 135297.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 = 0.00427 (650/152322) while in subpopulation NFE AF = 0.00705 (480/68038). AF 95% confidence interval is 0.00653. There are 4 homozygotes in GnomAd4. There are 276 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 4 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET2	NM_001127208.3	MANE Select	c.5152G>T	p.Val1718Leu	missense	Exon 11 of 11	NP_001120680.1	Q6N021-1
	TET2-AS1	NR_126420.1		n.318+58724C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TET2	ENST00000380013.9	TSL:5 MANE Select	c.5152G>T	p.Val1718Leu	missense	Exon 11 of 11	ENSP00000369351.4	Q6N021-1
TET2	ENST00000513237.5	TSL:1	c.5215G>T	p.Val1739Leu	missense	Exon 11 of 11	ENSP00000425443.1	E7EQS8
TET2	ENST00000540549.5	TSL:1	c.5152G>T	p.Val1718Leu	missense	Exon 11 of 11	ENSP00000442788.1	Q6N021-1

Frequencies

GnomAD3 genomes

AF:

0.00427

AC:

650

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00162

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00536

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00705

Gnomad OTH

AF:

0.00430

GnomAD2 exomes

AF:

0.00361

AC:

569

AN:

157498

AF XY:

0.00365

show subpopulations

Gnomad AFR exome

AF:

0.000977

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00497

Gnomad NFE exome

AF:

0.00668

Gnomad OTH exome

AF:

0.00247

GnomAD4 exome

AF:

0.00675

AC:

9450

AN:

1399634

Hom.:

Cov.:

AF XY:

0.00652

AC XY:

4502

AN XY:

690306

show subpopulations

African (AFR)

AF:

0.00101

AC:

AN:

31598

American (AMR)

AF:

0.00123

AC:

AN:

35708

Ashkenazi Jewish (ASJ)

AF:

0.000159

AC:

AN:

25180

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.00126

AC:

100

AN:

79236

European-Finnish (FIN)

AF:

0.00557

AC:

275

AN:

49388

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00806

AC:

8697

AN:

1078998

Other (OTH)

AF:

0.00511

AC:

297

AN:

58090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

566

1132

1699

2265

2831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

342

684

1026

1368

1710

<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:

0.00427

AC:

650

AN:

152322

Hom.:

Cov.:

AF XY:

0.00371

AC XY:

276

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

41572

American (AMR)

AF:

0.00196

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00145

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00536

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00705

AC:

480

AN:

68038

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

101

135

169

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00587

Hom.:

Bravo

AF:

0.00399

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.00804

AC:

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.00660

AC:

ExAC

AF:

0.00266

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

TET2-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.25

(source)

DANN

Benign

0.41

DEOGEN2

Benign

0.010

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.61

M_CAP

Benign

0.021

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

PhyloP100

-0.029

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.34

REVEL

Benign

0.0050

Sift

Benign

0.38

Sift4G

Benign

1.0

Polyphen

0.0070

Vest4

0.044

MutPred

0.25

Gain of catalytic residue at V1739 (P = 0.0405)

MVP

0.22

MPC

0.070

ClinPred

0.00035

GERP RS

-2.3

Varity_R

0.018

gMVP

0.30

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over