rs8128227

Positions:

• chr21-38822370-C-A

Variant summary

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

The NM_005239.6(ETS2):​c.1195-304C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0453 in 152,294 control chromosomes in the GnomAD database, including 215 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 0.045 (215 hom., cov: 33)
• Consequence: ETS2 NM_005239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -6.24

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETS2	NM_005239.6	c.1195-304C>A		intron_variant		ENST00000360938.8	NP_005230.1
ETS2	NM_001256295.2	c.1615-304C>A		intron_variant			NP_001243224.1
ETS2	XM_005260935.2	c.1195-304C>A		intron_variant			XP_005260992.1
ETS2	XM_017028290.2	c.1195-304C>A		intron_variant			XP_016883779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETS2	ENST00000360938.8	c.1195-304C>A		intron_variant		1	NM_005239.6	ENSP00000354194	P1
ETS2-AS1	ENST00000663561.1	n.535-8945G>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0453 AC: 6900 AN: 152176 Hom.: 215 Cov.: 33

Gnomad AFR AF: 0.0144

Gnomad AMI AF: 0.0769

Gnomad AMR AF: 0.0470

Gnomad ASJ AF: 0.0576

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0162

Gnomad FIN AF: 0.0322

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0701

Gnomad OTH AF: 0.0517

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0453 AC: 6899 AN: 152294 Hom.: 215 Cov.: 33 AF XY: 0.0431 AC XY: 3211 AN XY: 74476

Gnomad4 AFR AF: 0.0143

Gnomad4 AMR AF: 0.0469

Gnomad4 ASJ AF: 0.0576

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0160

Gnomad4 FIN AF: 0.0322

Gnomad4 NFE AF: 0.0702

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0513 Hom.: 30

Bravo AF: 0.0461

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.0010
DANN	Benign	0.32

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: rs8128227; hg19: chr21-40194294;