rs142312318

Variant names:

• chr4-105275662-G-A
• rs142312318
• NM_001127208.3:c.5152G>A

Your query was ambiguous. Multiple possible variants found:

• chr4-105275662-G-A
• chr4-105275662-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001127208.3(TET2):​c.5152G>A​(p.Val1718Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000286 in 1,399,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V1718L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: TET2 NM_001127208.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0290
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04673311).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TET2	NM_001127208.3	c.5152G>A	p.Val1718Ile	missense_variant	Exon 11 of 11	ENST00000380013.9	NP_001120680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TET2	ENST00000380013.9	c.5152G>A	p.Val1718Ile	missense_variant	Exon 11 of 11	5	NM_001127208.3	ENSP00000369351.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000286 AC: 4 AN: 1399640 Hom.: 0 Cov.: 32 AF XY: 0.00000145 AC XY: 1 AN XY: 690310

African (AFR) AF: 0.00 AC: 0 AN: 31598

American (AMR) AF: 0.00 AC: 0 AN: 35708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25180

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00000371 AC: 4 AN: 1079004

Other (OTH) AF: 0.00 AC: 0 AN: 58090

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.20
DANN	Benign	0.65
DEOGEN2	Benign	0.0078	T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.58	T;T;.
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.047	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.6	.;L;L
PhyloP100		-0.029
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.23	N;N;N
REVEL	Benign	0.015
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.52	T;T;T
Polyphen		0.028	B;B;B
Vest4		0.042
MutPred		0.21		Gain of helix (P = 0.132);.;.;
MVP		0.19
MPC		0.059
ClinPred		0.084	T
GERP RS		-2.3
Varity_R		0.012
gMVP		0.18
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs142312318; hg19: chr4-106196819;