rs199640757

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001127208.3(TET2):​c.1724C>A​(p.Ala575Glu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

TET2
NM_001127208.3 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.10
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]

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ACMG classification

Classification made for transcript

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=0.16016182).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TET2NM_001127208.3 linkuse as main transcriptc.1724C>A p.Ala575Glu missense_variant 3/11 ENST00000380013.9 NP_001120680.1
TET2-AS1NR_126420.1 linkuse as main transcriptn.319-57994G>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TET2ENST00000380013.9 linkuse as main transcriptc.1724C>A p.Ala575Glu missense_variant 3/115 NM_001127208.3 ENSP00000369351 A2Q6N021-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.43
CADD
Benign
7.9
DANN
Uncertain
0.98
DEOGEN2
Benign
0.016
.;T;T;T;.
Eigen
Benign
-0.12
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.27
N
LIST_S2
Benign
0.68
T;T;T;.;T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.16
T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.3
M;.;M;M;.
MutationTaster
Benign
1.0
N;N;N;N;N;N;N
PrimateAI
Benign
0.30
T
PROVEAN
Benign
-1.5
N;N;N;N;N
REVEL
Benign
0.17
Sift
Uncertain
0.0050
D;T;T;T;D
Sift4G
Benign
0.35
T;T;T;T;T
Polyphen
0.95
P;P;P;P;.
Vest4
0.22
MutPred
0.38
.;Gain of solvent accessibility (P = 0.0145);.;.;.;
MVP
0.51
MPC
0.20
ClinPred
0.35
T
GERP RS
4.7
Varity_R
0.14
gMVP
0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-106156823; API