Genetic Variant ETS2:c.*672T>C (chr21-38823561-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005239.6(ETS2):c.*672T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.574 in 152,250 control chromosomes in the GnomAD database, including 25,687 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 0.57 ( 25645 hom., cov: 33)

Exomes 𝑓: 0.57 ( 42 hom. )

Consequence

ETS2
NM_005239.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.698

Publications

11 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.817 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ETS2	NM_005239.6 link	c.*672T>C	3_prime_UTR_variant	Exon 10 of 10	ENST00000360938.8	NP_005230.1	P15036
ETS2	NM_001256295.2 link	c.*672T>C	3_prime_UTR_variant	Exon 11 of 11		NP_001243224.1
ETS2	XM_005260935.2 link	c.*672T>C	3_prime_UTR_variant	Exon 10 of 10		XP_005260992.1	P15036
ETS2	XM_017028290.2 link	c.*672T>C	3_prime_UTR_variant	Exon 10 of 10		XP_016883779.1	P15036

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETS2	ENST00000360938.8 link	c.*672T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_005239.6	ENSP00000354194.3		P15036

Frequencies

GnomAD3 genomes

AF:

0.574

AC:

87176

AN:

151868

Hom.:

25597

Cov.:

show subpopulations

Gnomad AFR

AF:

0.606

Gnomad AMI

AF:

0.449

Gnomad AMR

AF:

0.655

Gnomad ASJ

AF:

0.451

Gnomad EAS

AF:

0.782

Gnomad SAS

AF:

0.839

Gnomad FIN

AF:

0.620

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.504

Gnomad OTH

AF:

0.539

GnomAD4 exome

AF:

0.568

AC:

150

AN:

264

Hom.:

Cov.:

AF XY:

0.584

AC XY:

AN XY:

166

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.574

AC:

147

AN:

256

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.574

AC:

87281

AN:

151986

Hom.:

25645

Cov.:

AF XY:

0.585

AC XY:

43436

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.607

AC:

25134

AN:

41440

American (AMR)

AF:

0.656

AC:

10025

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.451

AC:

1564

AN:

3470

East Asian (EAS)

AF:

0.782

AC:

4058

AN:

5186

South Asian (SAS)

AF:

0.839

AC:

4048

AN:

4826

European-Finnish (FIN)

AF:

0.620

AC:

6519

AN:

10510

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.504

AC:

34241

AN:

67944

Other (OTH)

AF:

0.541

AC:

1144

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1900

3801

5701

7602

9502

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

752

1504

2256

3008

3760

<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:

0.535

Hom.:

10180

Bravo

AF:

0.569

Asia WGS

AF:

0.778

AC:

2699

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.1

(source)

DANN

Benign

0.73

PhyloP100

0.70

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over