chr4-105234016-G-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001127208.3(TET2):c.74G>T(p.Cys25Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
TET2
NM_001127208.3 missense
NM_001127208.3 missense
Scores
7
12
Clinical Significance
Conservation
PhyloP100: 3.69
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=0.24463174).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TET2 | NM_001127208.3 | c.74G>T | p.Cys25Phe | missense_variant | 3/11 | ENST00000380013.9 | |
TET2-AS1 | NR_126420.1 | n.319-56344C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TET2 | ENST00000380013.9 | c.74G>T | p.Cys25Phe | missense_variant | 3/11 | 5 | NM_001127208.3 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152102Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251050Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135664
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461790Hom.: 0 Cov.: 33 AF XY: 0.0000151 AC XY: 11AN XY: 727192
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152102Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74318
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 27, 2023 | This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 25 of the TET2 protein (p.Cys25Phe). This variant is present in population databases (rs762289112, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with TET2-related conditions. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;.;T;T
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;M;.;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Benign
T;D;D;D;T;T
Polyphen
D;P;P;P;.;.
Vest4
MutPred
0.23
.;Gain of relative solvent accessibility (P = 0.0905);.;.;.;.;
MVP
MPC
0.40
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at