Variant 4-105234028-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

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:2O:1

Conservation

PhyloP100: 0.849

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:):

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=0.0011830032).

BP6

Variant 4-105234028-C-G is Benign according to our data. Variant chr4-105234028-C-G is described in ClinVar as [Benign]. Clinvar id 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/exons	MANE	UniProt
TET2	NM_001127208.3 linkuse as main transcript	c.86C>G	p.Pro29Arg	missense_variant	3/11	ENST00000380013.9
TET2-AS1	NR_126420.1 linkuse as main transcript	n.319-56356G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TET2	ENST00000380013.9 linkuse as main transcript	c.86C>G	p.Pro29Arg	missense_variant	3/11	5	NM_001127208.3	A2	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

GnomAD3 exomes

AF:

0.0629

AC:

15788

AN:

250816

Hom.:

878

AF XY:

0.0625

AC XY:

8470

AN XY:

135524

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 SAS exome

AF:

0.115

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

Gnomad4 AFR exome

AF:

0.0329

Gnomad4 AMR exome

AF:

0.109

Gnomad4 ASJ exome

AF:

0.0362

Gnomad4 EAS exome

AF:

0.203

Gnomad4 SAS exome

AF:

0.117

Gnomad4 FIN exome

AF:

0.0657

Gnomad4 NFE exome

AF:

0.0126

Gnomad4 OTH exome

AF:

0.0405

GnomAD4 genome

AF:

0.0398

AC:

6057

AN:

152260

Hom.:

281

Cov.:

AF XY:

0.0448

AC XY:

3334

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0299

Gnomad4 AMR

AF:

0.0730

Gnomad4 ASJ

AF:

0.0308

Gnomad4 EAS

AF:

0.196

Gnomad4 SAS

AF:

0.121

Gnomad4 FIN

AF:

0.0691

Gnomad4 NFE

AF:

0.0170

Gnomad4 OTH

AF:

0.0430

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:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1Other:1

not provided, no classification provided	reference population	ITMI	Sep 19, 2013	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jan 24, 2024	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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

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

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;.;.

MutationTaster

Benign

0.98

P;P;P;P;P;P;P

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

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