rs587778703

Variant names:

• chr4-105276424-G-C
• rs587778703
• NM_001127208.3:c.5914G>C

Your query was ambiguous. Multiple possible variants found:

• chr4-105276424-G-C
• chr4-105276424-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001127208.3(TET2):​c.5914G>C​(p.Ala1972Pro) 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. Variant has been reported in ClinVar as not provided (no stars).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TET2 NM_001127208.3 missense
• Clinical Significance: not provided no classification provided O:1
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.4234277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TET2	NM_001127208.3	c.5914G>C	p.Ala1972Pro	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>C	p.Ala1972Pro	missense_variant	Exon 11 of 11	5	NM_001127208.3	ENSP00000369351.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not specified Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.72
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.18
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.062	T;T;T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.38	N
LIST_S2	Uncertain	0.88	D;D;.
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	.;M;M
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.71	N;N;N
REVEL	Benign	0.18
Sift	Benign	0.030	D;D;D
Sift4G	Benign	0.14	T;T;T
Polyphen		0.94	P;P;P
Vest4		0.65
MutPred		0.40		Gain of disorder (P = 0.0593);.;.;
MVP		0.41
MPC		0.36
ClinPred		0.42	T
GERP RS		2.3
Varity_R		0.066
gMVP		0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs587778703; hg19: chr4-106197581;