Genetic Variant NM_005239.6:c.*1015T>C (chr21-38823904-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.*1015T>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 0.34 in 152,186 control chromosomes in the GnomAD database, including 8,800 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 ( 8774 hom., cov: 32)

Exomes 𝑓: 0.38 ( 26 hom. )

Consequence

ETS2
NM_005239.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0940

Publications

6 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=-0.87).

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	UniProt
ETS2	NM_005239.6 link	c.*1015T>C	3_prime_UTR_variant	Exon 10 of 10	ENST00000360938.8	NP_005230.1	P15036
ETS2	NM_001256295.2 link	c.*1015T>C	3_prime_UTR_variant	Exon 11 of 11		NP_001243224.1
ETS2	XM_005260935.2 link	c.*1015T>C	3_prime_UTR_variant	Exon 10 of 10		XP_005260992.1	P15036
ETS2	XM_017028290.2 link	c.*1015T>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.*1015T>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_005239.6	ENSP00000354194.3		P15036

Frequencies

GnomAD3 genomes

AF:

0.340

AC:

51558

AN:

151682

Hom.:

8768

Cov.:

show subpopulations

Gnomad AFR

AF:

0.314

Gnomad AMI

AF:

0.353

Gnomad AMR

AF:

0.346

Gnomad ASJ

AF:

0.313

Gnomad EAS

AF:

0.271

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.365

Gnomad MID

AF:

0.328

Gnomad NFE

AF:

0.357

Gnomad OTH

AF:

0.329

GnomAD4 exome

AF:

0.376

AC:

145

AN:

386

Hom.:

Cov.:

AF XY:

0.397

AC XY:

AN XY:

224

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:

0.379

AC:

144

AN:

380

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.340

AC:

51596

AN:

151800

Hom.:

8774

Cov.:

AF XY:

0.339

AC XY:

25126

AN XY:

74176

show subpopulations

African (AFR)

AF:

0.314

AC:

12989

AN:

41394

American (AMR)

AF:

0.346

AC:

5281

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

1086

AN:

3468

East Asian (EAS)

AF:

0.271

AC:

1400

AN:

5168

South Asian (SAS)

AF:

0.340

AC:

1638

AN:

4818

European-Finnish (FIN)

AF:

0.365

AC:

3846

AN:

10526

Middle Eastern (MID)

AF:

0.322

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.357

AC:

24248

AN:

67864

Other (OTH)

AF:

0.329

AC:

693

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1756

3512

5268

7024

8780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

512

1024

1536

2048

2560

<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:

0.345

Hom.:

3574

Bravo

AF:

0.334

Asia WGS

AF:

0.304

AC:

1054

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

(source)

DANN

Benign

0.68

PhyloP100

0.094

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