rs141442603

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001127208.3(TET2):c.5449C>A(p.His1817Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000425 in 1,551,812 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00025 ( 2 hom. )

Consequence

TET2
NM_001127208.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.494

Publications

9 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058350265).

BP6

Variant 4-105275959-C-A is Benign according to our data. Variant chr4-105275959-C-A is described in ClinVar as Benign. ClinVar VariationId is 135293.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00204 (310/152268) while in subpopulation AFR AF = 0.00724 (301/41554). AF 95% confidence interval is 0.00657. There are 1 homozygotes in GnomAd4. There are 138 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET2	NM_001127208.3	MANE Select	c.5449C>A	p.His1817Asn	missense	Exon 11 of 11	NP_001120680.1
	TET2-AS1	NR_126420.1		n.318+58427G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
TET2	ENST00000380013.9	TSL:5 MANE Select	c.5449C>A	p.His1817Asn	missense	Exon 11 of 11	ENSP00000369351.4
TET2	ENST00000513237.5	TSL:1	c.5512C>A	p.His1838Asn	missense	Exon 11 of 11	ENSP00000425443.1
TET2	ENST00000540549.5	TSL:1	c.5449C>A	p.His1817Asn	missense	Exon 11 of 11	ENSP00000442788.1

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

310

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000414

AC:

AN:

157054

AF XY:

0.000385

show subpopulations

Gnomad AFR exome

AF:

0.00644

Gnomad AMR exome

AF:

0.000243

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000164

Gnomad OTH exome

AF:

0.000226

GnomAD4 exome

AF:

0.000250

AC:

350

AN:

1399544

Hom.:

Cov.:

AF XY:

0.000240

AC XY:

166

AN XY:

690286

show subpopulations

African (AFR)

AF:

0.00807

AC:

255

AN:

31598

American (AMR)

AF:

0.000252

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.000151

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49344

Middle Eastern (MID)

AF:

0.00176

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

1078980

Other (OTH)

AF:

0.000551

AC:

AN:

58064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

109

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00204

AC:

310

AN:

152268

Hom.:

Cov.:

AF XY:

0.00185

AC XY:

138

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.00724

AC:

301

AN:

41554

American (AMR)

AF:

0.000196

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.00218

Hom.:

Bravo

AF:

0.00225

ESP6500AA

AF:

0.00723

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000856

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Other:1

Sep 19, 2013

ITMI

Significance:not provided

Review Status:no classification provided

Collection Method:reference population

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.31

(source)

DANN

Benign

0.30

DEOGEN2

Benign

0.0098

Eigen

Benign

-0.85

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.45

MetaRNN

Benign

0.0058

MetaSVM

Benign

-0.90

MutationAssessor

Benign

1.6

PhyloP100

0.49

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.72

REVEL

Benign

0.021

Sift

Benign

1.0

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.065

MVP

0.19

MPC

0.077

ClinPred

0.0026

GERP RS

2.3

Varity_R

0.047

gMVP

0.28

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over