4-105272837-T-C

Position:

• chr4-105272837-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.4456T>C​(p.Ser1486Pro) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as other (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TET2 NM_001127208.3 missense
• Clinical Significance: other no assertion criteria provided O:1
• Conservation: PhyloP100: -0.0220

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=0.093625695).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TET2	NM_001127208.3	c.4456T>C	p.Ser1486Pro	missense_variant	10/11	ENST00000380013.9	NP_001120680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9	c.4456T>C	p.Ser1486Pro	missense_variant	10/11	5	NM_001127208.3	ENSP00000369351.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: other

Submissions summary: Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Nephroblastoma Other:1

other, no assertion criteria provided

clinical testing

Donald Williams Parsons Laboratory, Baylor College of Medicine

May 01, 2016

- 3: Mutations in other consensus cancer genes, not currently considered targetable

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;T;T
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.72	T;T;.
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.094	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	.;L;L
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.015	D;D;D
Sift4G	Benign	0.27	T;T;T
Polyphen		0.90	P;P;P
Vest4		0.25
MutPred		0.19		Loss of phosphorylation at S1507 (P = 0.01);.;.;
MVP		0.33
MPC		0.11
ClinPred		0.26	T
GERP RS		-4.9
Varity_R		0.095
gMVP		0.28

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1553918194; hg19: chr4-106193994; COSMIC: COSV54398602;