Variant 21-38814331-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_005239.6(ETS2):c.243A>G(p.Gln81=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 1,614,148 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 7 hom. )

Consequence

ETS2
NM_005239.6 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.509

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 made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 21-38814331-A-G is Benign according to our data. Variant chr21-38814331-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 771783.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.509 with no splicing effect.

BS2

High AC in GnomAd4 at 280 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
ETS2	NM_005239.6 linkuse as main transcript	c.243A>G	p.Gln81=	synonymous_variant	4/10	ENST00000360938.8
ETS2	NM_001256295.2 linkuse as main transcript	c.663A>G	p.Gln221=	synonymous_variant	5/11
ETS2	XM_005260935.2 linkuse as main transcript	c.243A>G	p.Gln81=	synonymous_variant	4/10
ETS2	XM_017028290.2 linkuse as main transcript	c.243A>G	p.Gln81=	synonymous_variant	4/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETS2	ENST00000360938.8 linkuse as main transcript	c.243A>G	p.Gln81=	synonymous_variant	4/10	1	NM_005239.6	P1
ETS2-AS1	ENST00000663561.1 linkuse as main transcript	n.535-906T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00184

AC:

280

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000579

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.000470

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00342

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00151

AC:

379

AN:

251432

Hom.:

AF XY:

0.00159

AC XY:

216

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.000665

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000425

Gnomad FIN exome

AF:

0.000554

Gnomad NFE exome

AF:

0.00265

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00233

AC:

3411

AN:

1461796

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

1620

AN XY:

727184

show subpopulations

Gnomad4 AFR exome

AF:

0.000388

Gnomad4 AMR exome

AF:

0.000514

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000406

Gnomad4 FIN exome

AF:

0.000581

Gnomad4 NFE exome

AF:

0.00284

Gnomad4 OTH exome

AF:

0.00248

GnomAD4 genome

AF:

0.00184

AC:

280

AN:

152352

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

116

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.000577

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.000470

Gnomad4 NFE

AF:

0.00342

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00226

Hom.:

Bravo

AF:

0.00142

EpiCase

AF:

0.00202

EpiControl

AF:

0.00284

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2022	ETS2: BP4, BP7 -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.9

DANN

Benign

0.43

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over