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

new If you want to explore the variant's impact on the transcript NM_005239.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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.

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.*672T>C		3_prime_UTR	Exon 10 of 10	NP_005230.1	P15036
	ETS2	NM_001256295.2		c.*672T>C		3_prime_UTR	Exon 11 of 11	NP_001243224.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ETS2	ENST00000360938.8	TSL:1 MANE Select	c.*672T>C	3_prime_UTR	Exon 10 of 10	ENSP00000354194.3	P15036
ETS2	ENST00000667466.1		c.*672T>C	3_prime_UTR	Exon 10 of 10	ENSP00000499540.1	A0A590UJP9
ETS2	ENST00000968691.1		c.*672T>C	3_prime_UTR	Exon 10 of 10	ENSP00000638750.1

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 v4.9

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over