chr21-38819507-T-G

Variant names:

• chr21-38819507-T-G
• rs457705
• NM_005239.6:c.816T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_005239.6(ETS2):​c.816T>G​(p.Thr272Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 1,612,886 control chromosomes in the GnomAD database, including 524,442 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 0.74 (42850 hom., cov: 31)
  • Exomes 𝑓: 0.80 (481592 hom.)
• Consequence: ETS2 NM_005239.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• Publications: 29 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP7: Synonymous conserved (PhyloP=-0.088 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.847 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.816T>G	p.Thr272Thr	synonymous	Exon 8 of 10	NP_005230.1	P15036
	ETS2	NM_001256295.2		c.1236T>G	p.Thr412Thr	synonymous	Exon 9 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.816T>G	p.Thr272Thr	synonymous	Exon 8 of 10	ENSP00000354194.3	P15036
	ETS2	ENST00000667466.1		c.816T>G	p.Thr272Thr	synonymous	Exon 8 of 10	ENSP00000499540.1	A0A590UJP9
	ETS2	ENST00000968691.1		c.840T>G	p.Thr280Thr	synonymous	Exon 8 of 10	ENSP00000638750.1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 112285 AN: 151874 Hom.: 42851 Cov.: 31

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.904

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.865

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.507

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.826

Gnomad NFE AF: 0.853

Gnomad OTH AF: 0.758

GnomAD2 exomes AF: 0.718 AC: 179825 AN: 250562 AF XY: 0.719

Gnomad AFR exome AF: 0.607

Gnomad AMR exome AF: 0.564

Gnomad ASJ exome AF: 0.853

Gnomad EAS exome AF: 0.472

Gnomad FIN exome AF: 0.752

Gnomad NFE exome AF: 0.852

Gnomad OTH exome AF: 0.772

GnomAD4 exome AF: 0.803 AC: 1173544 AN: 1460894 Hom.: 481592 Cov.: 49 AF XY: 0.796 AC XY: 578596 AN XY: 726650

African (AFR) AF: 0.598 AC: 20020 AN: 33460

American (AMR) AF: 0.576 AC: 25743 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 22231 AN: 26122

East Asian (EAS) AF: 0.450 AC: 17875 AN: 39686

South Asian (SAS) AF: 0.529 AC: 45623 AN: 86238

European-Finnish (FIN) AF: 0.754 AC: 40256 AN: 53408

Middle Eastern (MID) AF: 0.805 AC: 4640 AN: 5766

European-Non Finnish (NFE) AF: 0.855 AC: 950172 AN: 1111140

Other (OTH) AF: 0.778 AC: 46984 AN: 60364

GnomAD4 genome AF: 0.739 AC: 112313 AN: 151992 Hom.: 42850 Cov.: 31 AF XY: 0.728 AC XY: 54115 AN XY: 74320

African (AFR) AF: 0.615 AC: 25460 AN: 41406

American (AMR) AF: 0.685 AC: 10468 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.865 AC: 3003 AN: 3472

East Asian (EAS) AF: 0.459 AC: 2360 AN: 5144

South Asian (SAS) AF: 0.506 AC: 2438 AN: 4816

European-Finnish (FIN) AF: 0.749 AC: 7924 AN: 10578

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.853 AC: 58003 AN: 67984

Other (OTH) AF: 0.754 AC: 1589 AN: 2108

Alfa AF: 0.812 Hom.: 191712

Bravo AF: 0.732

Asia WGS AF: 0.495 AC: 1722 AN: 3478

EpiCase AF: 0.840

EpiControl AF: 0.848

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.1
DANN	Benign	0.65
PhyloP100		-0.088
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: rs457705; hg19: chr21-40191431; COSMIC: COSV62872557; COSMIC: COSV62872557;