rs12498609

Positions:

• chr4-105234028-C-A
• chr4-105234028-C-G
• chr4-105234028-C-T

Variant summary

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

The NM_001127208.3(TET2):​c.86C>A​(p.Pro29His) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P29R) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TET2 NM_001127208.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.849

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=0.11115664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TET2	NM_001127208.3	c.86C>A	p.Pro29His	missense_variant	3/11	ENST00000380013.9
TET2-AS1	NR_126420.1	n.319-56356G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TET2	ENST00000380013.9	c.86C>A	p.Pro29His	missense_variant	3/11	5	NM_001127208.3	A2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.085
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.025	.;T;T;T;.;.
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.046
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.68	T;T;T;.;T;T
M_CAP	Benign	0.0085	T
MetaRNN	Benign	0.11	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M;.;M;M;.;.
MutationTaster	Benign	0.99	N;N;N;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Uncertain	-3.0	D;D;D;D;D;D
REVEL	Benign	0.038
Sift	Benign	0.070	T;T;T;T;T;T
Sift4G	Benign	0.16	T;T;T;T;T;D
Polyphen		0.58	P;B;B;B;.;.
Vest4		0.20
MutPred		0.27		.;Gain of helix (P = 0.0425);.;.;.;.;
MVP		0.56
MPC		0.093
ClinPred		0.35	T
GERP RS		4.5
Varity_R		0.15
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs12498609; hg19: chr4-106155185;