rs192553789

Positions:

• chr4-105236382-C-A
• chr4-105236382-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001127208.3(TET2):​c.2440C>A​(p.Arg814Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TET2 NM_001127208.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.59

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:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044991136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TET2	NM_001127208.3	c.2440C>A	p.Arg814Ser	missense_variant	3/11	ENST00000380013.9	NP_001120680.1
TET2-AS1	NR_126420.1	n.319-58710G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9	c.2440C>A	p.Arg814Ser	missense_variant	3/11	5	NM_001127208.3	ENSP00000369351	A2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461672 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727136

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	4.7
DANN	Benign	0.17
DEOGEN2	Benign	0.0054	.;T;T;T;.
Eigen	Benign	-0.95
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.35	T;T;T;.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.045	T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-2.3	N;.;N;N;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	1.3	N;N;N;N;N
REVEL	Benign	0.17
Sift	Benign	1.0	T;T;T;T;T
Sift4G	Benign	0.85	T;T;T;T;T
Polyphen		0.0	B;B;B;B;.
Vest4		0.043
MutPred		0.21		.;Loss of MoRF binding (P = 0.0269);.;.;.;
MVP		0.25
MPC		0.078
ClinPred		0.21	T
GERP RS		4.6
Varity_R		0.16
gMVP		0.17

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

Publications

LitVar

Other links and lift over

dbSNP: rs192553789; hg19: chr4-106157539;