TET2 p.Gly429Arg

Variant names:

• chr4-105235227-G-C
• NM_001127208.3:c.1285G>C
• TET2 p.Gly429Arg

Your query was ambiguous. Multiple possible variants found:

• chr4-105235227-G-C
• chr4-105235227-G-A
• chr4-105235227-GGA-CGT
• chr4-105235227-GGA-CGC
• chr4-105235227-GGA-CGG
• chr4-105235227-GGA-AGG

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001127208.3(TET2):​c.1285G>C​(p.Gly429Arg) 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. 14/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TET2 NM_001127208.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.763
• Publications: 0 publications found

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:41125): (TET2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13588524).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET2	NM_001127208.3	MANE Select	c.1285G>C	p.Gly429Arg	missense	Exon 3 of 11	NP_001120680.1	Q6N021-1
	TET2	NM_017628.4		c.1285G>C	p.Gly429Arg	missense	Exon 3 of 3	NP_060098.3	Q6N021-2
	TET2-AS1	NR_126420.1		n.319-57555C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TET2	ENST00000380013.9	TSL:5 MANE Select	c.1285G>C	p.Gly429Arg	missense	Exon 3 of 11	ENSP00000369351.4	Q6N021-1
	TET2	ENST00000513237.5	TSL:1	c.1348G>C	p.Gly450Arg	missense	Exon 3 of 11	ENSP00000425443.1	E7EQS8
	TET2	ENST00000540549.5	TSL:1	c.1285G>C	p.Gly429Arg	missense	Exon 3 of 11	ENSP00000442788.1	Q6N021-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.76
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.18
Sift	Benign	0.078	T
Sift4G	Benign	0.27	T
Varity_R		0.082
gMVP		0.17
Mutation Taster		=95/5	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr4-106156384;