NM_001127208.3:c.1819G>C

Variant names:

• chr4-105235761-G-C
• NM_001127208.3:c.1819G>C
• TET2 p.Gly607Arg

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.1819G>C​(p.Gly607Arg) variant causes a missense change. 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. Synonymous variant affecting the same amino acid position (i.e. G607G) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TET2 NM_001127208.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.21
• 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=0.1786496).

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.1819G>C	p.Gly607Arg	missense	Exon 3 of 11	NP_001120680.1	Q6N021-1
	TET2	NM_017628.4		c.1819G>C	p.Gly607Arg	missense	Exon 3 of 3	NP_060098.3	Q6N021-2
	TET2-AS1	NR_126420.1		n.319-58089C>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.1819G>C	p.Gly607Arg	missense	Exon 3 of 11	ENSP00000369351.4	Q6N021-1
	TET2	ENST00000513237.5	TSL:1	c.1882G>C	p.Gly628Arg	missense	Exon 3 of 11	ENSP00000425443.1	E7EQS8
	TET2	ENST00000540549.5	TSL:1	c.1819G>C	p.Gly607Arg	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	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.2
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.11
Sift	Benign	0.082	T
Sift4G	Benign	0.067	T
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.29
Mutation Taster		=91/9	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: chr4-106156918;