rs147836249
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001127208.3(TET2):c.2604T>G(p.Phe868Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,614,100 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0015 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 24 hom. )
Consequence
TET2
NM_001127208.3 missense
NM_001127208.3 missense
Scores
1
5
11
Clinical Significance
Conservation
PhyloP100: 0.403
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 Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.008369237).
BP6
?
Variant 4-105236546-T-G is Benign according to our data. Variant chr4-105236546-T-G is described in ClinVar as [Benign]. Clinvar id is 135324.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00148 (225/152304) while in subpopulation EAS AF= 0.0168 (87/5190). AF 95% confidence interval is 0.0139. There are 0 homozygotes in gnomad4. There are 143 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TET2 | NM_001127208.3 | c.2604T>G | p.Phe868Leu | missense_variant | 3/11 | ENST00000380013.9 | |
TET2-AS1 | NR_126420.1 | n.319-58874A>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TET2 | ENST00000380013.9 | c.2604T>G | p.Phe868Leu | missense_variant | 3/11 | 5 | NM_001127208.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00147 AC: 223AN: 152186Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00238 AC: 596AN: 250788Hom.: 6 AF XY: 0.00222 AC XY: 301AN XY: 135518
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GnomAD4 exome AF: 0.00120 AC: 1757AN: 1461796Hom.: 24 Cov.: 34 AF XY: 0.00117 AC XY: 848AN XY: 727196
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GnomAD4 genome ? AF: 0.00148 AC: 225AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.00192 AC XY: 143AN XY: 74476
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ClinVar
Significance: Benign
Submissions summary: Benign:2Other:1
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1Other:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 26, 2021 | - - |
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T;T;.;T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;M;M;.
MutationTaster
Benign
N;N;N;N;N;N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N
REVEL
Benign
Sift
Uncertain
D;D;D;D;D
Sift4G
Benign
T;T;T;T;T
Polyphen
B;B;B;B;.
Vest4
MutPred
0.31
.;Gain of disorder (P = 0.1304);.;.;.;
MVP
MPC
0.12
ClinPred
T
GERP RS
Varity_R
gMVP
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