dbSNP rs77688599: ETS2:c.304+123G>A (chr21-38814515-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_005239.6(ETS2):c.304+123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,217,990 control chromosomes in the GnomAD database, including 467 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 0.021 ( 48 hom., cov: 33)

Exomes 𝑓: 0.027 ( 419 hom. )

Consequence

ETS2
NM_005239.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.998

Publications

2 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=-0.83).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0211 (3218/152296) while in subpopulation NFE AF = 0.0305 (2074/68022). AF 95% confidence interval is 0.0294. There are 48 homozygotes in GnomAd4. There are 1539 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 3218 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ETS2	NM_005239.6 link	c.304+123G>A	intron_variant	Intron 4 of 9	ENST00000360938.8	NP_005230.1	P15036
ETS2	NM_001256295.2 link	c.724+123G>A	intron_variant	Intron 5 of 10		NP_001243224.1
ETS2	XM_005260935.2 link	c.304+123G>A	intron_variant	Intron 4 of 9		XP_005260992.1	P15036
ETS2	XM_017028290.2 link	c.304+123G>A	intron_variant	Intron 4 of 9		XP_016883779.1	P15036

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETS2	ENST00000360938.8 link	c.304+123G>A		intron_variant	Intron 4 of 9	1	NM_005239.6	ENSP00000354194.3		P15036

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3219

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00560

Gnomad AMI

AF:

0.0439

Gnomad AMR

AF:

0.0257

Gnomad ASJ

AF:

0.0231

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00683

Gnomad FIN

AF:

0.0275

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.0305

Gnomad OTH

AF:

0.0315

GnomAD4 exome

AF:

0.0271

AC:

28923

AN:

1065694

Hom.:

419

AF XY:

0.0267

AC XY:

14211

AN XY:

533162

show subpopulations

African (AFR)

AF:

0.00416

AC:

102

AN:

24528

American (AMR)

AF:

0.0192

AC:

531

AN:

27714

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

405

AN:

18750

East Asian (EAS)

AF:

0.0000552

AC:

AN:

36242

South Asian (SAS)

AF:

0.00673

AC:

430

AN:

63892

European-Finnish (FIN)

AF:

0.0320

AC:

1239

AN:

38746

Middle Eastern (MID)

AF:

0.0363

AC:

118

AN:

3252

European-Non Finnish (NFE)

AF:

0.0308

AC:

24781

AN:

805858

Other (OTH)

AF:

0.0282

AC:

1315

AN:

46712

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1419

2838

4256

5675

7094

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

832

1664

2496

3328

4160

<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:

0.0211

AC:

3218

AN:

152296

Hom.:

Cov.:

AF XY:

0.0207

AC XY:

1539

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00558

AC:

232

AN:

41572

American (AMR)

AF:

0.0256

AC:

392

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0231

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00684

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0275

AC:

292

AN:

10602

Middle Eastern (MID)

AF:

0.0274

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0305

AC:

2074

AN:

68022

Other (OTH)

AF:

0.0312

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

162

324

487

649

811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0269

Hom.:

102

Bravo

AF:

0.0208

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

1.7

(source)

DANN

Benign

0.51

PhyloP100

-1.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over