rs530

Positions:

• chr21-38823353-T-A
• chr21-38823353-T-C

Variant summary

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

The NM_005239.6(ETS2):​c.*464T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 152,838 control chromosomes in the GnomAD database, including 27,160 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 0.59 (27038 hom., cov: 33)
  • Exomes 𝑓: 0.60 (122 hom.)
• Consequence: ETS2 NM_005239.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.469

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=-0.58).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.819 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETS2	NM_005239.6	c.*464T>A		3_prime_UTR_variant	10/10	ENST00000360938.8	NP_005230.1
ETS2	NM_001256295.2	c.*464T>A		3_prime_UTR_variant	11/11		NP_001243224.1
ETS2	XM_005260935.2	c.*464T>A		3_prime_UTR_variant	10/10		XP_005260992.1
ETS2	XM_017028290.2	c.*464T>A		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.*464T>A		3_prime_UTR_variant	10/10	1	NM_005239.6	ENSP00000354194.3

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89376 AN: 152044 Hom.: 26986 Cov.: 33

Gnomad AFR AF: 0.653

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.840

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.552

GnomAD4 exome AF: 0.598 AC: 404 AN: 676 Hom.: 122 Cov.: 0 AF XY: 0.592 AC XY: 225 AN XY: 380

Gnomad4 AFR exome AF: 0.818

Gnomad4 AMR exome AF: 0.800

Gnomad4 ASJ exome AF: 0.600

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.600

Gnomad4 NFE exome AF: 0.534

Gnomad4 OTH exome AF: 0.571

GnomAD4 genome AF: 0.588 AC: 89486 AN: 152162 Hom.: 27038 Cov.: 33 AF XY: 0.598 AC XY: 44514 AN XY: 74398

Gnomad4 AFR AF: 0.653

Gnomad4 AMR AF: 0.659

Gnomad4 ASJ AF: 0.455

Gnomad4 EAS AF: 0.782

Gnomad4 SAS AF: 0.840

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.554

Alfa AF: 0.552 Hom.: 3166

Bravo AF: 0.585

Asia WGS AF: 0.782 AC: 2713 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.3
DANN	Benign	0.87

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: rs530; hg19: chr21-40195277;