Variant 4-105275672-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001127208.3(TET2):c.5162T>G(p.Leu1721Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,551,620 control chromosomes in the GnomAD database, including 11,862 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict 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 0.12 ( 1067 hom., cov: 32)

Exomes 𝑓: 0.12 ( 10795 hom. )

Consequence

TET2
NM_001127208.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.37

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013713539).

BP6

Variant 4-105275672-T-G is Benign according to our data. Variant chr4-105275672-T-G is described in ClinVar as [Benign]. Clinvar id is 135300.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TET2	NM_001127208.3 linkuse as main transcript	c.5162T>G	p.Leu1721Trp	missense_variant	11/11	ENST00000380013.9	NP_001120680.1	Q6N021-1A0A158SIU0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9 linkuse as main transcript	c.5162T>G	p.Leu1721Trp	missense_variant	11/11	5	NM_001127208.3	ENSP00000369351.4		Q6N021-1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17593

AN:

152018

Hom.:

1069

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0934

Gnomad AMI

AF:

0.136

Gnomad AMR

AF:

0.0932

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.0412

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.128

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.116

AC:

18189

AN:

157376

Hom.:

1139

AF XY:

0.118

AC XY:

9815

AN XY:

83076

show subpopulations

Gnomad AFR exome

AF:

0.0893

Gnomad AMR exome

AF:

0.0648

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.0400

Gnomad SAS exome

AF:

0.122

Gnomad FIN exome

AF:

0.174

Gnomad NFE exome

AF:

0.130

Gnomad OTH exome

AF:

0.126

GnomAD4 exome

AF:

0.122

AC:

170522

AN:

1399484

Hom.:

10795

Cov.:

AF XY:

0.123

AC XY:

84929

AN XY:

690236

show subpopulations

Gnomad4 AFR exome

AF:

0.0939

Gnomad4 AMR exome

AF:

0.0683

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.0349

Gnomad4 SAS exome

AF:

0.122

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.124

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.116

AC:

17594

AN:

152136

Hom.:

1067

Cov.:

AF XY:

0.118

AC XY:

8809

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0932

Gnomad4 AMR

AF:

0.0932

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.0411

Gnomad4 SAS

AF:

0.109

Gnomad4 FIN

AF:

0.184

Gnomad4 NFE

AF:

0.128

Gnomad4 OTH

AF:

0.122

Alfa

AF:

0.120

Hom.:

1883

Bravo

AF:

0.107

TwinsUK

AF:

0.120

AC:

446

ALSPAC

AF:

0.120

AC:

464

ESP6500AA

AF:

0.0968

AC:

134

ESP6500EA

AF:

0.135

AC:

429

ExAC

AF:

0.118

AC:

3007

Asia WGS

AF:

0.0600

AC:

208

AN:

3478

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

0.094

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.0067

T;T;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.10

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.73

T;T;.

MetaRNN

Benign

0.0014

T;T;T

MetaSVM

Benign

-0.63

MutationAssessor

Benign

0.90

.;L;L

PrimateAI

Benign

0.33

PROVEAN

Benign

0.030

N;N;N

REVEL

Benign

0.084

Sift

Uncertain

0.0030

D;D;D

Sift4G

Benign

0.23

T;T;T

Polyphen

0.79

P;P;P

Vest4

0.10

MPC

0.35

ClinPred

0.081

GERP RS

5.2

Varity_R

0.079

gMVP

0.62

Splicing

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