rs10010325

Positions:

• chr4-105185196-C-A
• chr4-105185196-C-G
• chr4-105185196-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127208.3(TET2):​c.-192-5164C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 151,020 control chromosomes in the GnomAD database, including 18,172 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18172 hom., cov: 29)
• Consequence: TET2 NM_001127208.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TET2	NM_001127208.3	c.-192-5164C>A		intron_variant		ENST00000380013.9
TET2-AS1	NR_126420.1	n.319-7524G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TET2	ENST00000380013.9	c.-192-5164C>A		intron_variant		5	NM_001127208.3	A2

Frequencies

GnomAD3 genomes AF: 0.490 AC: 73967 AN: 150902 Hom.: 18148 Cov.: 29

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.425

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.511

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.490 AC: 74033 AN: 151020 Hom.: 18172 Cov.: 29 AF XY: 0.489 AC XY: 36030 AN XY: 73722

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.550

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.425

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.516

Alfa AF: 0.488 Hom.: 29115

Bravo AF: 0.492

Asia WGS AF: 0.520 AC: 1807 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs10010325; hg19: chr4-106106353;