rs6517481

Variant names:

• chr21-38822384-A-G
• rs6517481
• NM_005239.6:c.1195-290A>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.1195-290A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.374 in 152,038 control chromosomes in the GnomAD database, including 10,790 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 0.37 (10790 hom., cov: 32)
• Consequence: ETS2 NM_005239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 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.1195-290A>G		intron	N/A	NP_005230.1	P15036
	ETS2	NM_001256295.2		c.1615-290A>G		intron	N/A	NP_001243224.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS2	ENST00000360938.8	TSL:1 MANE Select	c.1195-290A>G		intron	N/A	ENSP00000354194.3	P15036
	ETS2	ENST00000667466.1		c.1300-290A>G		intron	N/A	ENSP00000499540.1	A0A590UJP9
	ETS2	ENST00000968691.1		c.1219-290A>G		intron	N/A	ENSP00000638750.1

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56878 AN: 151920 Hom.: 10771 Cov.: 32

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.357

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.354

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.374 AC: 56938 AN: 152038 Hom.: 10790 Cov.: 32 AF XY: 0.373 AC XY: 27733 AN XY: 74306

African (AFR) AF: 0.399 AC: 16537 AN: 41462

American (AMR) AF: 0.362 AC: 5539 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1170 AN: 3470

East Asian (EAS) AF: 0.417 AC: 2144 AN: 5138

South Asian (SAS) AF: 0.357 AC: 1720 AN: 4816

European-Finnish (FIN) AF: 0.369 AC: 3913 AN: 10590

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24686 AN: 67964

Other (OTH) AF: 0.355 AC: 749 AN: 2112

Alfa AF: 0.378 Hom.: 1381

Bravo AF: 0.373

Asia WGS AF: 0.346 AC: 1202 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0070
DANN	Benign	0.45
PhyloP100		-1.1
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: rs6517481; hg19: chr21-40194308;