rs11700777

chr21-38814331-A-G

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.509

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-AS1 (HGNC:56712): (ETS2 antisense RNA 1)

ACMG classification

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 GnomAd at 280 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00184 AC: 280 AN: 152234 Hom.: 1 Cov.: 33

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.: 0 AF XY: 0.00159 AC XY: 216 AN XY: 135898

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.: 7 Cov.: 31 AF XY: 0.00223 AC XY: 1620 AN XY: 727184

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.: 1 Cov.: 33 AF XY: 0.00156 AC XY: 116 AN XY: 74500

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.: 1

Bravo AF: 0.00142

EpiCase AF: 0.00202

EpiControl AF: 0.00284

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2022	ETS2: BP4, BP7 -

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

Other links and lift over

dbSNP: rs11700777; hg19: chr21-40186255;