rs61744960

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001127208.3(TET2):c.1064G>A(p.Gly355Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0375 in 1,614,054 control chromosomes in the GnomAD database, including 1,339 homozygotes. In-silico tool predicts 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 0.028 ( 89 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1250 hom. )

Consequence

TET2
NM_001127208.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.90

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003620863).

BP6

Variant 4-105235006-G-A is Benign according to our data. Variant chr4-105235006-G-A is described in ClinVar as [Benign]. Clinvar id is 135317.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 = 0.0281 (4272/152256) while in subpopulation NFE AF= 0.0428 (2914/68022). AF 95% confidence interval is 0.0415. There are 89 homozygotes in gnomad4. There are 1958 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 89 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TET2	NM_001127208.3 link	c.1064G>A	p.Gly355Asp	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.1064G>A	p.Gly355Asp	missense_variant	Exon 3 of 11	5	NM_001127208.3	ENSP00000369351.4		Q6N021-1

Frequencies

GnomAD3 genomes

AF:

0.0281

AC:

4275

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00811

Gnomad AMI

AF:

0.0154

Gnomad AMR

AF:

0.0341

Gnomad ASJ

AF:

0.0372

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0193

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0428

Gnomad OTH

AF:

0.0368

GnomAD3 exomes

AF:

0.0288

AC:

7213

AN:

250800

Hom.:

162

AF XY:

0.0292

AC XY:

3963

AN XY:

135568

show subpopulations

Gnomad AFR exome

AF:

0.00683

Gnomad AMR exome

AF:

0.0274

Gnomad ASJ exome

AF:

0.0369

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0177

Gnomad FIN exome

AF:

0.0198

Gnomad NFE exome

AF:

0.0406

Gnomad OTH exome

AF:

0.0362

GnomAD4 exome

AF:

0.0384

AC:

56182

AN:

1461798

Hom.:

1250

Cov.:

AF XY:

0.0381

AC XY:

27696

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.00729

Gnomad4 AMR exome

AF:

0.0279

Gnomad4 ASJ exome

AF:

0.0365

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0169

Gnomad4 FIN exome

AF:

0.0185

Gnomad4 NFE exome

AF:

0.0442

Gnomad4 OTH exome

AF:

0.0333

GnomAD4 genome

AF:

0.0281

AC:

4272

AN:

152256

Hom.:

Cov.:

AF XY:

0.0263

AC XY:

1958

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.00809

Gnomad4 AMR

AF:

0.0341

Gnomad4 ASJ

AF:

0.0372

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.0193

Gnomad4 NFE

AF:

0.0428

Gnomad4 OTH

AF:

0.0360

Alfa

AF:

0.0389

Hom.:

188

Bravo

AF:

0.0291

TwinsUK

AF:

0.0415

AC:

154

ALSPAC

AF:

0.0490

AC:

189

ESP6500AA

AF:

0.00704

AC:

ESP6500EA

AF:

0.0437

AC:

376

ExAC

AF:

0.0267

AC:

3245

Asia WGS

AF:

0.00635

AC:

AN:

3478

EpiCase

AF:

0.0432

EpiControl

AF:

0.0461

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 26, 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

- -

TET2-related disorder

Benign:1

Sep 13, 2021

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

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

0.14

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.056

.;T;T;T;.

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.22

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

T;T;T;.;T

MetaRNN

Benign

0.0036

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.;M;M;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.0

N;N;N;N;N

REVEL

Benign

0.14

Sift

Uncertain

0.0020

D;D;D;D;D

Sift4G

Benign

0.79

T;T;T;T;T

Polyphen

0.94

P;P;P;P;.

Vest4

0.20

MPC

0.42

ClinPred

0.026

GERP RS

3.1

Varity_R

0.25

gMVP

0.19

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

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