rs1051475

Positions:

• chr21-38823904-T-C

Variant summary

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

The ENST00000360938.8(ETS2):​c.*1015T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,186 control chromosomes in the GnomAD database, including 8,800 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 (8774 hom., cov: 32)
  • Exomes 𝑓: 0.38 (26 hom.)
• Consequence: ETS2 ENST00000360938.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.354 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETS2	NM_005239.6	c.*1015T>C		3_prime_UTR_variant	10/10	ENST00000360938.8	NP_005230.1
ETS2	NM_001256295.2	c.*1015T>C		3_prime_UTR_variant	11/11		NP_001243224.1
ETS2	XM_005260935.2	c.*1015T>C		3_prime_UTR_variant	10/10		XP_005260992.1
ETS2	XM_017028290.2	c.*1015T>C		3_prime_UTR_variant	10/10		XP_016883779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETS2	ENST00000360938.8	c.*1015T>C		3_prime_UTR_variant	10/10	1	NM_005239.6	ENSP00000354194	P1
ETS2-AS1	ENST00000663561.1	n.535-10479A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51558 AN: 151682 Hom.: 8768 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.353

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.376 AC: 145 AN: 386 Hom.: 26 Cov.: 0 AF XY: 0.397 AC XY: 89 AN XY: 224

Gnomad4 FIN exome AF: 0.379

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.340 AC: 51596 AN: 151800 Hom.: 8774 Cov.: 32 AF XY: 0.339 AC XY: 25126 AN XY: 74176

Gnomad4 AFR AF: 0.314

Gnomad4 AMR AF: 0.346

Gnomad4 ASJ AF: 0.313

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.329

Alfa AF: 0.345 Hom.: 2830

Bravo AF: 0.334

Asia WGS AF: 0.304 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	11
DANN	Benign	0.68

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: rs1051475; hg19: chr21-40195828;