NM_005239.6:c.1194+400C>T

Variant names:

• chr21-38822104-C-T
• rs2070529
• NM_005239.6:c.1194+400C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005239.6(ETS2):​c.1194+400C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 151,990 control chromosomes in the GnomAD database, including 4,319 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 0.22 (4319 hom., cov: 32)
• Consequence: ETS2 NM_005239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.886
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005239.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS2	NM_005239.6	MANE Select	c.1194+400C>T		intron	N/A	NP_005230.1
	ETS2	NM_001256295.2		c.1614+400C>T		intron	N/A	NP_001243224.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS2	ENST00000360938.8	TSL:1 MANE Select	c.1194+400C>T		intron	N/A	ENSP00000354194.3
	ETS2	ENST00000667466.1		c.1299+400C>T		intron	N/A	ENSP00000499540.1
	ETS2	ENST00000968691.1		c.1218+400C>T		intron	N/A	ENSP00000638750.1

Frequencies

GnomAD3 genomes AF: 0.215 AC: 32696 AN: 151872 Hom.: 4307 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.293

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.215 AC: 32740 AN: 151990 Hom.: 4319 Cov.: 32 AF XY: 0.228 AC XY: 16959 AN XY: 74304

African (AFR) AF: 0.235 AC: 9735 AN: 41450

American (AMR) AF: 0.294 AC: 4493 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3468

East Asian (EAS) AF: 0.491 AC: 2520 AN: 5128

South Asian (SAS) AF: 0.496 AC: 2388 AN: 4812

European-Finnish (FIN) AF: 0.252 AC: 2667 AN: 10576

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.146 AC: 9923 AN: 67974

Other (OTH) AF: 0.198 AC: 418 AN: 2108

Alfa AF: 0.178 Hom.: 4163

Bravo AF: 0.215

Asia WGS AF: 0.462 AC: 1605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.4
DANN	Benign	0.83
PhyloP100		0.89
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2070529; hg19: chr21-40194028;