rs2070531

Variant names:

• chr21-38822292-C-T
• rs2070531
• NM_005239.6:c.1195-382C>T

Variant summary

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

The NM_005239.6(ETS2):​c.1195-382C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,092 control chromosomes in the GnomAD database, including 9,135 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 0.34 (9135 hom., cov: 32)
• Consequence: ETS2 NM_005239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.172
• Publications: 9 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS2	NM_005239.6	c.1195-382C>T		intron_variant	Intron 9 of 9	ENST00000360938.8	NP_005230.1
ETS2	NM_001256295.2	c.1615-382C>T		intron_variant	Intron 10 of 10		NP_001243224.1
ETS2	XM_005260935.2	c.1195-382C>T		intron_variant	Intron 9 of 9		XP_005260992.1
ETS2	XM_017028290.2	c.1195-382C>T		intron_variant	Intron 9 of 9		XP_016883779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETS2	ENST00000360938.8	c.1195-382C>T		intron_variant	Intron 9 of 9	1	NM_005239.6	ENSP00000354194.3

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52289 AN: 151974 Hom.: 9131 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.353

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.362

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.344 AC: 52317 AN: 152092 Hom.: 9135 Cov.: 32 AF XY: 0.343 AC XY: 25475 AN XY: 74358

African (AFR) AF: 0.314 AC: 13006 AN: 41464

American (AMR) AF: 0.353 AC: 5397 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1160 AN: 3472

East Asian (EAS) AF: 0.271 AC: 1400 AN: 5166

South Asian (SAS) AF: 0.348 AC: 1675 AN: 4812

European-Finnish (FIN) AF: 0.370 AC: 3915 AN: 10590

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.362 AC: 24602 AN: 67984

Other (OTH) AF: 0.323 AC: 683 AN: 2112

Alfa AF: 0.348 Hom.: 17356

Bravo AF: 0.338

Asia WGS AF: 0.300 AC: 1041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.40
PhyloP100		0.17
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: rs2070531; hg19: chr21-40194216;