21-38823135-A-G

Variant names:

• chr21-38823135-A-G
• rs711
• NM_005239.6:c.*246A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.534
• Publications: 16 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 -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.

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.*246A>G		3_prime_UTR	Exon 10 of 10	NP_005230.1	P15036
	ETS2	NM_001256295.2		c.*246A>G		3_prime_UTR	Exon 11 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.*246A>G		3_prime_UTR	Exon 10 of 10	ENSP00000354194.3	P15036
	ETS2	ENST00000667466.1		c.*246A>G		3_prime_UTR	Exon 10 of 10	ENSP00000499540.1	A0A590UJP9
	ETS2	ENST00000968691.1		c.*246A>G		3_prime_UTR	Exon 10 of 10	ENSP00000638750.1

Frequencies

GnomAD3 genomes AF: 0.577 AC: 87730 AN: 152012 Hom.: 25934 Cov.: 33

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.: 3 AF XY: 0.560 AC XY: 56570 AN XY: 101004

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

GnomAD4 genome AF: 0.577 AC: 87839 AN: 152130 Hom.: 25985 Cov.: 33 AF XY: 0.588 AC XY: 43756 AN XY: 74392

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.39
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs711; hg19: chr21-40195059; COSMIC: COSV62873232; COSMIC: COSV62873232;