rs2070530

Positions:

• chr21-38822185-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005239.6(ETS2):​c.1194+481G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,112 control chromosomes in the GnomAD database, including 4,520 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 0.22 (4520 hom., cov: 33)
• Consequence: ETS2 NM_005239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.664

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]

ENSG00000205622 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.481 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETS2	NM_005239.6	c.1194+481G>C		intron_variant		ENST00000360938.8	NP_005230.1
ETS2	NM_001256295.2	c.1614+481G>C		intron_variant			NP_001243224.1
ETS2	XM_005260935.2	c.1194+481G>C		intron_variant			XP_005260992.1
ETS2	XM_017028290.2	c.1194+481G>C		intron_variant			XP_016883779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETS2	ENST00000360938.8	c.1194+481G>C		intron_variant		1	NM_005239.6	ENSP00000354194.3

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33546 AN: 151994 Hom.: 4505 Cov.: 33

Gnomad AFR AF: 0.253

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.210

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

GnomAD4 genome AF: 0.221 AC: 33601 AN: 152112 Hom.: 4520 Cov.: 33 AF XY: 0.233 AC XY: 17358 AN XY: 74368

Gnomad4 AFR AF: 0.253

Gnomad4 AMR AF: 0.298

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.493

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.252

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.212

Alfa AF: 0.185 Hom.: 383

Bravo AF: 0.221

Asia WGS AF: 0.465 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.44

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

Publications

LitVar

Other links and lift over

dbSNP: rs2070530; hg19: chr21-40194109;