rs73450556

Positions:

• chr21-38814487-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005239.6(ETS2):​c.304+95G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,485,990 control chromosomes in the GnomAD database, including 29 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 0.0070 (13 hom., cov: 33)
  • Exomes 𝑓: 0.00095 (16 hom.)
• Consequence: ETS2 NM_005239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.125

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=-0.84).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00703 (1071/152302) while in subpopulation AFR AF= 0.0229 (952/41560). AF 95% confidence interval is 0.0217. There are 13 homozygotes in gnomad4. There are 490 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1071 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETS2	NM_005239.6	c.304+95G>T		intron_variant		ENST00000360938.8	NP_005230.1
ETS2	NM_001256295.2	c.724+95G>T		intron_variant			NP_001243224.1
ETS2	XM_005260935.2	c.304+95G>T		intron_variant			XP_005260992.1
ETS2	XM_017028290.2	c.304+95G>T		intron_variant			XP_016883779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETS2	ENST00000360938.8	c.304+95G>T		intron_variant		1	NM_005239.6	ENSP00000354194	P1
ETS2-AS1	ENST00000663561.1	n.535-1062C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00703 AC: 1070 AN: 152184 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.000954 AC: 1273 AN: 1333688 Hom.: 16 AF XY: 0.000863 AC XY: 573 AN XY: 663816

Gnomad4 AFR exome AF: 0.0240

Gnomad4 AMR exome AF: 0.00334

Gnomad4 ASJ exome AF: 0.0000441

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000143

Gnomad4 FIN exome AF: 0.000254

Gnomad4 NFE exome AF: 0.000269

Gnomad4 OTH exome AF: 0.00196

GnomAD4 genome AF: 0.00703 AC: 1071 AN: 152302 Hom.: 13 Cov.: 33 AF XY: 0.00658 AC XY: 490 AN XY: 74472

Gnomad4 AFR AF: 0.0229

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000441

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00555 Hom.: 4

Bravo AF: 0.00782

Asia WGS AF: 0.000866 AC: 4 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.7
DANN	Benign	0.45

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: rs73450556; hg19: chr21-40186411;