rs539389221

chr4-105275815-G-Achr4-105275815-G-C

Variant summary

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

The NM_001127208.3(TET2):c.5305G>A(p.Ala1769Thr) 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A1769P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: TET2 NM_001127208.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.00

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 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=0.08015522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TET2	NM_001127208.3	c.5305G>A	p.Ala1769Thr	missense_variant	11/11	ENST00000380013.9
TET2-AS1	NR_126420.1	n.318+58571C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TET2	ENST00000380013.9	c.5305G>A	p.Ala1769Thr	missense_variant	11/11	5	NM_001127208.3	A2
TET2	ENST00000513237.5	c.5368G>A	p.Ala1790Thr	missense_variant	11/11	1		P4
TET2	ENST00000540549.5	c.5305G>A	p.Ala1769Thr	missense_variant	11/11	1		A2
TET2	ENST00000265149.9	c.*1629G>A		3_prime_UTR_variant, NMD_transcript_variant	10/10	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
Cadd	Benign	9.7
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0090	T;T;T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.68	T;T;.
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.080	T;T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.2	N;N;N
REVEL	Benign	0.021
Sift	Benign	0.093	T;T;T
Sift4G	Benign	0.23	T;T;T
Polyphen		0.25	B;B;B
Vest4		0.34
MutPred		0.16		Gain of glycosylation at A1790 (P = 0.0237);.;.;
MVP		0.35
MPC		0.11
ClinPred		0.14	T
GERP RS		3.4
Varity_R		0.049
gMVP		0.47

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs539389221; hg19: chr4-106196972;