Genetic Variant ETS2:c.*1575C>T (chr21-38824464-C-T) – 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.*1575C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,546 control chromosomes in the GnomAD database, including 8,912 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 0.34 ( 8893 hom., cov: 32)

Exomes 𝑓: 0.25 ( 19 hom. )

Consequence

ETS2
NM_005239.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.42

Publications

18 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=-0.76).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
ETS2	NM_005239.6 link	c.*1575C>T	3_prime_UTR_variant	Exon 10 of 10	ENST00000360938.8	NP_005230.1
ETS2	NM_001256295.2 link	c.*1575C>T	3_prime_UTR_variant	Exon 11 of 11		NP_001243224.1
ETS2	XM_005260935.2 link	c.*1575C>T	3_prime_UTR_variant	Exon 10 of 10		XP_005260992.1
ETS2	XM_017028290.2 link	c.*1575C>T	3_prime_UTR_variant	Exon 10 of 10		XP_016883779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETS2	ENST00000360938.8 link	c.*1575C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_005239.6	ENSP00000354194.3

Frequencies

GnomAD3 genomes

AF:

0.341

AC:

51757

AN:

151862

Hom.:

8886

Cov.:

show subpopulations

Gnomad AFR

AF:

0.315

Gnomad AMI

AF:

0.354

Gnomad AMR

AF:

0.347

Gnomad ASJ

AF:

0.314

Gnomad EAS

AF:

0.273

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.368

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.358

Gnomad OTH

AF:

0.330

GnomAD4 exome

AF:

0.250

AC:

142

AN:

568

Hom.:

Cov.:

AF XY:

0.243

AC XY:

AN XY:

296

show subpopulations

African (AFR)

AF:

0.200

AC:

AN:

American (AMR)

AF:

0.125

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.167

AC:

AN:

East Asian (EAS)

AF:

0.150

AC:

AN:

100

South Asian (SAS)

AF:

0.333

AC:

AN:

European-Finnish (FIN)

AF:

0.313

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.276

AC:

AN:

312

Other (OTH)

AF:

0.225

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

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:

0.341

AC:

51798

AN:

151978

Hom.:

8893

Cov.:

AF XY:

0.340

AC XY:

25237

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.315

AC:

13035

AN:

41430

American (AMR)

AF:

0.347

AC:

5300

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.314

AC:

1089

AN:

3472

East Asian (EAS)

AF:

0.273

AC:

1411

AN:

5162

South Asian (SAS)

AF:

0.340

AC:

1642

AN:

4826

European-Finnish (FIN)

AF:

0.368

AC:

3875

AN:

10532

Middle Eastern (MID)

AF:

0.322

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.358

AC:

24334

AN:

67970

Other (OTH)

AF:

0.330

AC:

697

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1759

3518

5277

7036

8795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

514

1028

1542

2056

2570

<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:

0.346

Hom.:

35660

Bravo

AF:

0.334

Asia WGS

AF:

0.305

AC:

1057

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.31

(source)

DANN

Benign

0.92

PhyloP100

-2.4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over