Variant 4-105234042-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001127208.3(TET2):c.100C>T(p.Leu34Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0168 in 1,614,044 control chromosomes in the GnomAD database, including 305 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 0.014 ( 30 hom., cov: 32)

Exomes 𝑓: 0.017 ( 275 hom. )

Consequence

TET2
NM_001127208.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 0.997

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051226914).

BP6

Variant 4-105234042-C-T is Benign according to our data. Variant chr4-105234042-C-T is described in ClinVar as [Benign]. Clinvar id is 135308.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-105234042-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0138 (2100/152276) while in subpopulation SAS AF= 0.0189 (91/4822). AF 95% confidence interval is 0.0173. There are 30 homozygotes in gnomad4. There are 1029 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TET2	NM_001127208.3 linkuse as main transcript	c.100C>T	p.Leu34Phe	missense_variant	3/11	ENST00000380013.9
TET2-AS1	NR_126420.1 linkuse as main transcript	n.319-56370G>A		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.100C>T	p.Leu34Phe	missense_variant	3/11	5	NM_001127208.3	A2	Q6N021-1

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

2097

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00350

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.0482

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0186

Gnomad FIN

AF:

0.0201

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0181

Gnomad OTH

AF:

0.0182

GnomAD3 exomes

AF:

0.0156

AC:

3919

AN:

250992

Hom.:

AF XY:

0.0167

AC XY:

2268

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.00314

Gnomad AMR exome

AF:

0.00706

Gnomad ASJ exome

AF:

0.0439

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0159

Gnomad FIN exome

AF:

0.0195

Gnomad NFE exome

AF:

0.0191

Gnomad OTH exome

AF:

0.0168

GnomAD4 exome

AF:

0.0171

AC:

24945

AN:

1461768

Hom.:

275

Cov.:

AF XY:

0.0174

AC XY:

12657

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00269

Gnomad4 AMR exome

AF:

0.00749

Gnomad4 ASJ exome

AF:

0.0442

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0167

Gnomad4 FIN exome

AF:

0.0182

Gnomad4 NFE exome

AF:

0.0177

Gnomad4 OTH exome

AF:

0.0186

GnomAD4 genome

AF:

0.0138

AC:

2100

AN:

152276

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1029

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00351

Gnomad4 AMR

AF:

0.0112

Gnomad4 ASJ

AF:

0.0482

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0189

Gnomad4 FIN

AF:

0.0201

Gnomad4 NFE

AF:

0.0181

Gnomad4 OTH

AF:

0.0180

Alfa

AF:

0.0180

Hom.:

Bravo

AF:

0.0123

TwinsUK

AF:

0.0181

AC:

ALSPAC

AF:

0.0218

AC:

ESP6500AA

AF:

0.00522

AC:

ESP6500EA

AF:

0.0190

AC:

163

ExAC

AF:

0.0153

AC:

1853

Asia WGS

AF:

0.00606

AC:

AN:

3478

EpiCase

AF:

0.0185

EpiControl

AF:

0.0192

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.029

.;T;T;T;.;.

Eigen

Benign

-0.097

Eigen_PC

Benign

0.046

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.78

T;T;T;.;T;T

MetaRNN

Benign

0.0051

T;T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Uncertain

2.4

M;.;M;M;.;.

MutationTaster

Benign

0.72

D;D;D;D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-1.7

N;N;N;N;N;D

REVEL

Benign

0.037

Sift

Pathogenic

0.0

D;D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.23

B;B;B;B;.;.

Vest4

0.22

MPC

0.18

ClinPred

0.058

GERP RS

4.6

Varity_R

0.29

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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