4-105236382-C-G

Variant names:

• chr4-105236382-C-G
• rs192553789
• NM_001127208.3:c.2440C>G

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.2440C>G​(p.Arg814Gly) 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. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R814H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TET2 NM_001127208.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.59
• 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=0.124301106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TET2	NM_001127208.3	c.2440C>G	p.Arg814Gly	missense_variant	Exon 3 of 11	ENST00000380013.9	NP_001120680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9	c.2440C>G	p.Arg814Gly	missense_variant	Exon 3 of 11	5	NM_001127208.3	ENSP00000369351.4

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	0.069
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.0080	.;T;T;T;.
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.63	T;T;T;.;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.12	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.0	N;.;N;N;.
PhyloP100		5.6
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.12	N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.037	D;D;D;D;D
Sift4G	Benign	0.36	T;T;T;T;T
Polyphen		0.0010	B;B;B;B;.
Vest4		0.070
MutPred		0.18		.;Loss of solvent accessibility (P = 0.0193);.;.;.;
MVP		0.41
MPC		0.088
ClinPred		0.71	D
GERP RS		4.6
Varity_R		0.16
gMVP		0.19
Mutation Taster		=98/2	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

Other links and lift over

dbSNP: rs192553789; hg19: chr4-106157539;