rs1051476

chr21-38823912-C-Gchr21-38823912-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.*1023C>G 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 152,124 control chromosomes in the GnomAD database, including 8,788 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 (8763 hom., cov: 32)
  • Exomes 𝑓: 0.37 (25 hom.)
• Consequence: ETS2 NM_005239.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.103

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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETS2	NM_005239.6	c.*1023C>G		3_prime_UTR_variant	10/10	ENST00000360938.8
ETS2	NM_001256295.2	c.*1023C>G		3_prime_UTR_variant	11/11
ETS2	XM_005260935.2	c.*1023C>G		3_prime_UTR_variant	10/10
ETS2	XM_017028290.2	c.*1023C>G		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETS2	ENST00000360938.8	c.*1023C>G		3_prime_UTR_variant	10/10	1	NM_005239.6	P1
ETS2-AS1	ENST00000663561.1	n.535-10487G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51531 AN: 151608 Hom.: 8756 Cov.: 32

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.367 AC: 146 AN: 398 Hom.: 25 Cov.: 0 AF XY: 0.384 AC XY: 89 AN XY: 232

Gnomad4 FIN exome AF: 0.368

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.340 AC: 51572 AN: 151726 Hom.: 8763 Cov.: 32 AF XY: 0.339 AC XY: 25109 AN XY: 74126

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: 0.330

Alfa AF: 0.212 Hom.: 484

Bravo AF: 0.334

Asia WGS AF: 0.305 AC: 1059 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	0.64
Dann	Benign	0.63

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: rs1051476; hg19: chr21-40195836;