rs34373350

Variant names:

Variant summary

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

The NM_005239.6(ETS2):c.190G>A(p.Ala64Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,613,808 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0084 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 11 hom. )

Consequence

ETS2
NM_005239.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0690

Publications

7 publications found

Variant links:

Genes affected

ETS2 (HGNC:3489): (ETS proto-oncogene 2, transcription factor) This gene encodes a transcription factor which regulates genes involved in development and apoptosis. The encoded protein is also a protooncogene and shown to be involved in regulation of telomerase. A pseudogene of this gene is located on the X chromosome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ETS2 links:

ETS2-AS1 (HGNC:56712): (ETS2 antisense RNA 1)

ETS2-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 (MetaRNN=0.003026694).

BP6

Variant 21-38814278-G-A is Benign according to our data. Variant chr21-38814278-G-A is described in ClinVar as Benign. ClinVar VariationId is 786688.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 = 0.0084 (1278/152180) while in subpopulation AFR AF = 0.0251 (1043/41508). AF 95% confidence interval is 0.0239. There are 12 homozygotes in GnomAd4. There are 601 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1278 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005239.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS2	NM_005239.6	MANE Select	c.190G>A	p.Ala64Thr	missense	Exon 4 of 10	NP_005230.1	P15036
	ETS2	NM_001256295.2		c.610G>A	p.Ala204Thr	missense	Exon 5 of 11	NP_001243224.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ETS2	ENST00000360938.8	TSL:1 MANE Select	c.190G>A	p.Ala64Thr	missense	Exon 4 of 10	ENSP00000354194.3	P15036
ETS2	ENST00000667466.1		c.190G>A	p.Ala64Thr	missense	Exon 4 of 10	ENSP00000499540.1	A0A590UJP9
ETS2	ENST00000968691.1		c.190G>A	p.Ala64Thr	missense	Exon 4 of 10	ENSP00000638750.1

Frequencies

GnomAD3 genomes

AF:

0.00833

AC:

1267

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0249

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00452

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00219

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00305

AC:

767

AN:

251236

AF XY:

0.00255

show subpopulations

Gnomad AFR exome

AF:

0.0262

Gnomad AMR exome

AF:

0.00211

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000462

Gnomad NFE exome

AF:

0.00210

Gnomad OTH exome

AF:

0.00277

GnomAD4 exome

AF:

0.00266

AC:

3882

AN:

1461628

Hom.:

Cov.:

AF XY:

0.00250

AC XY:

1817

AN XY:

727130

show subpopulations

African (AFR)

AF:

0.0226

AC:

757

AN:

33468

American (AMR)

AF:

0.00237

AC:

106

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.000544

AC:

AN:

53350

Middle Eastern (MID)

AF:

0.00156

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00253

AC:

2810

AN:

1111882

Other (OTH)

AF:

0.00273

AC:

165

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

179

359

538

718

897

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

240

360

480

600

<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:

0.00840

AC:

1278

AN:

152180

Hom.:

Cov.:

AF XY:

0.00808

AC XY:

601

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.0251

AC:

1043

AN:

41508

American (AMR)

AF:

0.00451

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000208

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.000283

AC:

AN:

10590

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00219

AC:

149

AN:

68006

Other (OTH)

AF:

0.00568

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

112

169

225

281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00426

Hom.:

Bravo

AF:

0.00901

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.0243

AC:

107

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00346

AC:

420

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00164

EpiControl

AF:

0.00130

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.93

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.33

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.67

MetaRNN

Benign

0.0030

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.069

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.14

REVEL

Benign

0.0080

Sift

Benign

0.52

Sift4G

Benign

0.57

Polyphen

0.0010

Vest4

0.024

MVP

0.56

MPC

0.31

ClinPred

0.0030

GERP RS

-7.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.013

gMVP

0.16

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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