4-105234139-T-C

Position:

• chr4-105234139-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001127208.3(TET2):​c.197T>C​(p.Met66Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M66L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TET2 NM_001127208.3 missense
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: -0.204

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-AS1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08156809).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TET2	NM_001127208.3	c.197T>C	p.Met66Thr	missense_variant	3/11	ENST00000380013.9
TET2-AS1	NR_126420.1	n.319-56467A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TET2	ENST00000380013.9	c.197T>C	p.Met66Thr	missense_variant	3/11	5	NM_001127208.3	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

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	0.12
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.14
DANN	Benign	0.40
DEOGEN2	Benign	0.020	.;T;T;T;.;.
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.47	T;T;T;.;T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.082	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M;.;M;M;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N;N;N;N;N;D
REVEL	Benign	0.022
Sift	Benign	0.25	T;T;T;T;T;T
Sift4G	Benign	0.55	T;T;T;T;T;T
Polyphen		0.051	B;B;B;B;.;.
Vest4		0.18
MutPred		0.29		.;Loss of stability (P = 0.0351);.;.;.;.;
MVP		0.32
MPC		0.080
ClinPred		0.80	D
GERP RS		2.4
Varity_R		0.093
gMVP		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs587778709; hg19: chr4-106155296;