4-105276424-G-T

Variant names:

• chr4-105276424-G-T
• NM_001127208.3:c.5914G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001127208.3(TET2):​c.5914G>T​(p.Ala1972Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,399,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 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: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TET2 NM_001127208.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.91

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08457002).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TET2	NM_001127208.3	c.5914G>T	p.Ala1972Ser	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.5914G>T	p.Ala1972Ser	missense_variant	Exon 11 of 11	5	NM_001127208.3	ENSP00000369351.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1399640 Hom.: 0 Cov.: 34 AF XY: 0.00000145 AC XY: 1 AN XY: 690304

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: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	11
DANN	Benign	0.94
DEOGEN2	Benign	0.0072	T;T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.68
FATHMM_MKL	Benign	0.35	N
LIST_S2	Uncertain	0.88	D;D;.
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.085	T;T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Uncertain	2.1	.;M;M
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.30	N;N;N
REVEL	Benign	0.031
Sift	Benign	0.069	T;T;T
Sift4G	Benign	0.087	T;T;T
Polyphen		0.52	P;P;P
Vest4		0.23
MutPred		0.27		Gain of phosphorylation at A1993 (P = 0.0417);.;.;
MVP		0.23
MPC		0.081
ClinPred		0.14	T
GERP RS		2.3
Varity_R		0.024
gMVP		0.42

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: chr4-106197581;