Variant 4-105275327-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001127208.3(TET2):c.4817G>A(p.Gly1606Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000322 in 1,551,698 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

TET2
NM_001127208.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.16

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TET2	NM_001127208.3 linkuse as main transcript	c.4817G>A	p.Gly1606Asp	missense_variant	11/11	ENST00000380013.9	NP_001120680.1
TET2-AS1	NR_126420.1 linkuse as main transcript	n.318+59059C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9 linkuse as main transcript	c.4817G>A	p.Gly1606Asp	missense_variant	11/11	5	NM_001127208.3	ENSP00000369351	A2	Q6N021-1
TET2	ENST00000513237.5 linkuse as main transcript	c.4880G>A	p.Gly1627Asp	missense_variant	11/11	1		ENSP00000425443	P4
TET2	ENST00000540549.5 linkuse as main transcript	c.4817G>A	p.Gly1606Asp	missense_variant	11/11	1		ENSP00000442788	A2	Q6N021-1
TET2	ENST00000265149.9 linkuse as main transcript	c.*1141G>A		3_prime_UTR_variant, NMD_transcript_variant	10/10	5		ENSP00000265149		Q6N021-3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000286

AC:

AN:

1399570

Hom.:

Cov.:

AF XY:

0.00000435

AC XY:

AN XY:

690274

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152128

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74320

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.087

T;T;T

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.79

LIST_S2

Benign

0.78

T;T;.

M_CAP

Benign

0.048

MetaRNN

Uncertain

0.47

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.3

.;M;M

MutationTaster

Benign

0.96

D;D;D;D

PrimateAI

Benign

0.33

PROVEAN

Benign

-2.2

N;N;N

REVEL

Benign

0.12

Sift

Uncertain

0.0040

D;D;D

Sift4G

Benign

0.80

T;T;T

Polyphen

1.0

D;D;D

Vest4

0.49

MutPred

0.16

Loss of catalytic residue at A1626 (P = 0.035);.;.;

MVP

0.52

MPC

0.43

ClinPred

0.90

GERP RS

3.4

Varity_R

0.22

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over