Variant 21-38814372-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005239.6(ETS2):c.284G>A(p.Arg95Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00014 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

ETS2
NM_005239.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98

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:

ENSG00000205622 (HGNC:):

ENSG00000205622 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.056150883).

BS2

High AC in GnomAd4 at 16 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETS2	NM_005239.6 linkuse as main transcript	c.284G>A	p.Arg95Gln	missense_variant	4/10	ENST00000360938.8	NP_005230.1	P15036
ETS2	NM_001256295.2 linkuse as main transcript	c.704G>A	p.Arg235Gln	missense_variant	5/11		NP_001243224.1
ETS2	XM_005260935.2 linkuse as main transcript	c.284G>A	p.Arg95Gln	missense_variant	4/10		XP_005260992.1	P15036
ETS2	XM_017028290.2 linkuse as main transcript	c.284G>A	p.Arg95Gln	missense_variant	4/10		XP_016883779.1	P15036

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETS2	ENST00000360938.8 linkuse as main transcript	c.284G>A	p.Arg95Gln	missense_variant	4/10	1	NM_005239.6	ENSP00000354194.3		P15036

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000115

AC:

AN:

251338

Hom.:

AF XY:

0.000125

AC XY:

AN XY:

135856

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000144

AC:

210

AN:

1461792

Hom.:

Cov.:

AF XY:

0.000143

AC XY:

104

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.000291

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000167

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000105

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000140

Hom.:

Bravo

AF:

0.0000793

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.000382

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.284G>A (p.R95Q) alteration is located in exon 4 (coding exon 3) of the ETS2 gene. This alteration results from a G to A substitution at nucleotide position 284, causing the arginine (R) at amino acid position 95 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.25

T;T;.;T

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.52

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.58

T;.;T;T

M_CAP

Benign

0.0098

MetaRNN

Benign

0.056

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.31

N;N;.;.

MutationTaster

Benign

0.65

N;N

PrimateAI

Benign

0.32

PROVEAN

Benign

0.85

N;N;N;N

REVEL

Benign

0.15

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.59

T;T;T;T

Polyphen

0.048

B;B;.;D

Vest4

0.063

MVP

0.72

MPC

0.80

ClinPred

0.061

GERP RS

4.0

Varity_R

0.14

gMVP

0.21

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over