rs1553918194

Positions:

• chr4-105272837-T-A
• chr4-105272837-T-C

Variant summary

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

The NM_001127208.3(TET2):​c.4456T>A​(p.Ser1486Thr) 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. 14/20 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)
• Consequence: TET2 NM_001127208.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0220

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=0.031821996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TET2	NM_001127208.3	c.4456T>A	p.Ser1486Thr	missense_variant	10/11	ENST00000380013.9	NP_001120680.1
TET2-AS1	NR_126420.1	n.318+61549A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9	c.4456T>A	p.Ser1486Thr	missense_variant	10/11	5	NM_001127208.3	ENSP00000369351	A2
TET2	ENST00000513237.5	c.4519T>A	p.Ser1507Thr	missense_variant	10/11	1		ENSP00000425443	P4
TET2	ENST00000540549.5	c.4456T>A	p.Ser1486Thr	missense_variant	10/11	1		ENSP00000442788	A2
TET2	ENST00000265149.9	c.*780T>A		3_prime_UTR_variant, NMD_transcript_variant	9/10	5		ENSP00000265149

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.6
DANN	Benign	0.86
DEOGEN2	Benign	0.010	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.66	T;T;.
M_CAP	Benign	0.0045	T
MetaRNN	Benign	0.032	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.69	.;N;N
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.40	N;N;N
REVEL	Benign	0.036
Sift	Benign	0.28	T;T;T
Sift4G	Benign	0.42	T;T;T
Polyphen		0.0040	B;B;B
Vest4		0.10
MutPred		0.17		Loss of helix (P = 0.0444);.;.;
MVP		0.23
MPC		0.067
ClinPred		0.029	T
GERP RS		-4.9
Varity_R		0.028
gMVP		0.21

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-106193994;