Genetic Variant ETS2:c.304+95G>T (chr21-38814487-G-T) – 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+95G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,485,990 control chromosomes in the GnomAD database, including 29 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 0.0070 ( 13 hom., cov: 33)

Exomes 𝑓: 0.00095 ( 16 hom. )

Consequence

ETS2
NM_005239.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.125

Publications

1 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=-0.84).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00703 (1071/152302) while in subpopulation AFR AF = 0.0229 (952/41560). AF 95% confidence interval is 0.0217. There are 13 homozygotes in GnomAd4. There are 490 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1071 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
ETS2	NM_005239.6 link	c.304+95G>T	intron_variant	Intron 4 of 9	ENST00000360938.8	NP_005230.1	P15036
ETS2	NM_001256295.2 link	c.724+95G>T	intron_variant	Intron 5 of 10		NP_001243224.1
ETS2	XM_005260935.2 link	c.304+95G>T	intron_variant	Intron 4 of 9		XP_005260992.1	P15036
ETS2	XM_017028290.2 link	c.304+95G>T	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+95G>T		intron_variant	Intron 4 of 9	1	NM_005239.6	ENSP00000354194.3		P15036

Frequencies

GnomAD3 genomes

AF:

0.00703

AC:

1070

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0229

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00484

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000441

Gnomad OTH

AF:

0.00574

GnomAD4 exome

AF:

0.000954

AC:

1273

AN:

1333688

Hom.:

AF XY:

0.000863

AC XY:

573

AN XY:

663816

show subpopulations

African (AFR)

AF:

0.0240

AC:

728

AN:

30278

American (AMR)

AF:

0.00334

AC:

127

AN:

38050

Ashkenazi Jewish (ASJ)

AF:

0.0000441

AC:

AN:

22692

East Asian (EAS)

AF:

0.00

AC:

AN:

38842

South Asian (SAS)

AF:

0.000143

AC:

AN:

76826

European-Finnish (FIN)

AF:

0.000254

AC:

AN:

47206

Middle Eastern (MID)

AF:

0.00270

AC:

AN:

4072

European-Non Finnish (NFE)

AF:

0.000269

AC:

274

AN:

1020060

Other (OTH)

AF:

0.00196

AC:

109

AN:

55662

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

114

170

227

284

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00703

AC:

1071

AN:

152302

Hom.:

Cov.:

AF XY:

0.00658

AC XY:

490

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.0229

AC:

952

AN:

41560

American (AMR)

AF:

0.00484

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000441

AC:

AN:

68034

Other (OTH)

AF:

0.00568

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

109

164

218

273

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00619

Hom.:

Bravo

AF:

0.00782

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.7

(source)

DANN

Benign

0.45

PhyloP100

0.13

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