rs11700777

Variant names:

• chr21-38814331-A-G
• rs11700777
• NM_005239.6:c.243A>G
• ETS2 p.Gln81Gln

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_005239.6(ETS2):​c.243A>G​(p.Gln81Gln) 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:3
• Conservation: PhyloP100: -0.509
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005239.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS2	NM_005239.6	MANE Select	c.243A>G	p.Gln81Gln	synonymous	Exon 4 of 10	NP_005230.1	P15036
	ETS2	NM_001256295.2		c.663A>G	p.Gln221Gln	synonymous	Exon 5 of 11	NP_001243224.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS2	ENST00000360938.8	TSL:1 MANE Select	c.243A>G	p.Gln81Gln	synonymous	Exon 4 of 10	ENSP00000354194.3	P15036
	ETS2	ENST00000667466.1		c.243A>G	p.Gln81Gln	synonymous	Exon 4 of 10	ENSP00000499540.1	A0A590UJP9
	ETS2	ENST00000968691.1		c.243A>G	p.Gln81Gln	synonymous	Exon 4 of 10	ENSP00000638750.1

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

GnomAD2 exomes AF: 0.00151 AC: 379 AN: 251432 AF XY: 0.00159

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 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

African (AFR) AF: 0.000388 AC: 13 AN: 33480

American (AMR) AF: 0.000514 AC: 23 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39698

South Asian (SAS) AF: 0.000406 AC: 35 AN: 86258

European-Finnish (FIN) AF: 0.000581 AC: 31 AN: 53348

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 0.00284 AC: 3155 AN: 1111994

Other (OTH) AF: 0.00248 AC: 150 AN: 60392

GnomAD4 genome AF: 0.00184 AC: 280 AN: 152352 Hom.: 1 Cov.: 33 AF XY: 0.00156 AC XY: 116 AN XY: 74500

African (AFR) AF: 0.000577 AC: 24 AN: 41578

American (AMR) AF: 0.000784 AC: 12 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000828 AC: 4 AN: 4832

European-Finnish (FIN) AF: 0.000470 AC: 5 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00342 AC: 233 AN: 68038

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00226 Hom.: 1

Bravo AF: 0.00142

EpiCase AF: 0.00202

EpiControl AF: 0.00284

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.9
DANN	Benign	0.43
PhyloP100		-0.51
Mutation Taster		=98/2	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs11700777; hg19: chr21-40186255;