dbSNP rs146373819: TET2:p.Arg13Arg (chr4-105233979-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001127208.3(TET2):c.37A>C(p.Arg13Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.000421 in 1,614,122 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00025 ( 2 hom. )

Consequence

TET2
NM_001127208.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 5.74

Publications

2 publications found

Variant links:

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 links:

TET2-AS1 (HGNC:41125): (TET2 antisense RNA 1)

TET2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 4-105233979-A-C is Benign according to our data. Variant chr4-105233979-A-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 2044059.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00202 (308/152348) while in subpopulation AFR AF = 0.00719 (299/41590). AF 95% confidence interval is 0.00652. There are 1 homozygotes in GnomAd4. There are 137 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 2 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127208.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TET2	NM_001127208.3	MANE Select	c.37A>C	p.Arg13Arg	synonymous	Exon 3 of 11	NP_001120680.1	Q6N021-1
TET2	NM_017628.4		c.37A>C	p.Arg13Arg	synonymous	Exon 3 of 3	NP_060098.3	Q6N021-2
TET2-AS1	NR_126420.1		n.319-56307T>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TET2	ENST00000380013.9	TSL:5 MANE Select	c.37A>C	p.Arg13Arg	synonymous	Exon 3 of 11	ENSP00000369351.4	Q6N021-1
TET2	ENST00000513237.5	TSL:1	c.100A>C	p.Arg34Arg	synonymous	Exon 3 of 11	ENSP00000425443.1	E7EQS8
TET2	ENST00000540549.5	TSL:1	c.37A>C	p.Arg13Arg	synonymous	Exon 3 of 11	ENSP00000442788.1	Q6N021-1

Frequencies

GnomAD3 genomes

AF:

0.00202

AC:

308

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00721

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000486

AC:

122

AN:

251056

AF XY:

0.000354

show subpopulations

Gnomad AFR exome

AF:

0.00646

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.000254

AC:

371

AN:

1461774

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

174

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.00809

AC:

271

AN:

33480

American (AMR)

AF:

0.000201

AC:

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.000162

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000306

AC:

AN:

1111980

Other (OTH)

AF:

0.000546

AC:

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00202

AC:

308

AN:

152348

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

137

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00719

AC:

299

AN:

41590

American (AMR)

AF:

0.000196

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68038

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00215

Hom.:

Bravo

AF:

0.00224

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.9

(source)

DANN

Benign

0.61

PhyloP100

5.7

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over