rs11254

Positions:

• chr21-38824464-C-T

Variant summary

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

The NM_005239.6(ETS2):​c.*1575C>T 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 152,546 control chromosomes in the GnomAD database, including 8,912 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 (8893 hom., cov: 32)
  • Exomes 𝑓: 0.25 (19 hom.)
• Consequence: ETS2 NM_005239.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.42

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=-0.76).
• 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.*1575C>T		3_prime_UTR_variant	10/10	ENST00000360938.8	NP_005230.1
ETS2	NM_001256295.2	c.*1575C>T		3_prime_UTR_variant	11/11		NP_001243224.1
ETS2	XM_005260935.2	c.*1575C>T		3_prime_UTR_variant	10/10		XP_005260992.1
ETS2	XM_017028290.2	c.*1575C>T		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.*1575C>T		3_prime_UTR_variant	10/10	1	NM_005239.6	ENSP00000354194	P1
ETS2-AS1	ENST00000663561.1	n.535-11039G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51757 AN: 151862 Hom.: 8886 Cov.: 32

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.354

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.314

Gnomad EAS AF: 0.273

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.358

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.250 AC: 142 AN: 568 Hom.: 19 Cov.: 0 AF XY: 0.243 AC XY: 72 AN XY: 296

Gnomad4 AFR exome AF: 0.200

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.167

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.333

Gnomad4 FIN exome AF: 0.313

Gnomad4 NFE exome AF: 0.276

Gnomad4 OTH exome AF: 0.225

GnomAD4 genome AF: 0.341 AC: 51798 AN: 151978 Hom.: 8893 Cov.: 32 AF XY: 0.340 AC XY: 25237 AN XY: 74282

Gnomad4 AFR AF: 0.315

Gnomad4 AMR AF: 0.347

Gnomad4 ASJ AF: 0.314

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.358

Gnomad4 OTH AF: 0.330

Alfa AF: 0.345 Hom.: 15840

Bravo AF: 0.334

Asia WGS AF: 0.305 AC: 1057 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.31
DANN	Benign	0.92

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: rs11254; hg19: chr21-40196388;