Genetic Variant NM_005239.6:c.*246A>G (chr21-38823135-A-G) – 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.*246A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.567 in 350,818 control chromosomes in the GnomAD database, including 58,082 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 0.58 ( 25985 hom., cov: 33)

Exomes 𝑓: 0.56 ( 32097 hom. )

Consequence

ETS2
NM_005239.6 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.534

Publications

16 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=-0.89).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.808 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ETS2	NM_005239.6 link	c.*246A>G	3_prime_UTR_variant	Exon 10 of 10	ENST00000360938.8	NP_005230.1	P15036
ETS2	NM_001256295.2 link	c.*246A>G	3_prime_UTR_variant	Exon 11 of 11		NP_001243224.1
ETS2	XM_005260935.2 link	c.*246A>G	3_prime_UTR_variant	Exon 10 of 10		XP_005260992.1	P15036
ETS2	XM_017028290.2 link	c.*246A>G	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.*246A>G		3_prime_UTR_variant	Exon 10 of 10	1	NM_005239.6	ENSP00000354194.3		P15036

Frequencies

GnomAD3 genomes

AF:

0.577

AC:

87730

AN:

152012

Hom.:

25934

Cov.:

show subpopulations

Gnomad AFR

AF:

0.621

Gnomad AMI

AF:

0.424

Gnomad AMR

AF:

0.656

Gnomad ASJ

AF:

0.463

Gnomad EAS

AF:

0.783

Gnomad SAS

AF:

0.830

Gnomad FIN

AF:

0.621

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.538

GnomAD4 exome

AF:

0.559

AC:

111074

AN:

198688

Hom.:

32097

Cov.:

AF XY:

0.560

AC XY:

56570

AN XY:

101004

show subpopulations

African (AFR)

AF:

0.617

AC:

3773

AN:

6116

American (AMR)

AF:

0.697

AC:

4207

AN:

6032

Ashkenazi Jewish (ASJ)

AF:

0.473

AC:

3610

AN:

7636

East Asian (EAS)

AF:

0.805

AC:

14057

AN:

17472

South Asian (SAS)

AF:

0.834

AC:

3733

AN:

4474

European-Finnish (FIN)

AF:

0.612

AC:

9206

AN:

15052

Middle Eastern (MID)

AF:

0.508

AC:

532

AN:

1048

European-Non Finnish (NFE)

AF:

0.507

AC:

64701

AN:

127576

Other (OTH)

AF:

0.546

AC:

7255

AN:

13282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

2199

4398

6597

8796

10995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.577

AC:

87839

AN:

152130

Hom.:

25985

Cov.:

AF XY:

0.588

AC XY:

43756

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.622

AC:

25804

AN:

41494

American (AMR)

AF:

0.656

AC:

10039

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.463

AC:

1605

AN:

3470

East Asian (EAS)

AF:

0.783

AC:

4051

AN:

5172

South Asian (SAS)

AF:

0.830

AC:

4005

AN:

4826

European-Finnish (FIN)

AF:

0.621

AC:

6566

AN:

10576

Middle Eastern (MID)

AF:

0.473

AC:

139

AN:

294

European-Non Finnish (NFE)

AF:

0.502

AC:

34102

AN:

67986

Other (OTH)

AF:

0.541

AC:

1142

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

1908

3816

5723

7631

9539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<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:

0.519

Hom.:

12021

Bravo

AF:

0.573

Asia WGS

AF:

0.779

AC:

2706

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.5

(source)

DANN

Benign

0.39

PhyloP100

-0.53

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