21-38821990-T-C

Variant names:

• chr21-38821990-T-C
• rs374575
• NM_005239.6:c.1194+286T>C

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+286T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.791 in 152,096 control chromosomes in the GnomAD database, including 48,595 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 0.79 (48595 hom., cov: 31)
• Consequence: ETS2 NM_005239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.932 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+286T>C		intron	N/A	NP_005230.1	P15036
	ETS2	NM_001256295.2		c.1614+286T>C		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+286T>C		intron	N/A	ENSP00000354194.3	P15036
	ETS2	ENST00000667466.1		c.1299+286T>C		intron	N/A	ENSP00000499540.1	A0A590UJP9
	ETS2	ENST00000968691.1		c.1218+286T>C		intron	N/A	ENSP00000638750.1

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120234 AN: 151978 Hom.: 48528 Cov.: 31

Gnomad AFR AF: 0.939

Gnomad AMI AF: 0.787

Gnomad AMR AF: 0.815

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.888

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.695

Gnomad OTH AF: 0.787

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

GnomAD4 genome AF: 0.791 AC: 120360 AN: 152096 Hom.: 48595 Cov.: 31 AF XY: 0.793 AC XY: 58968 AN XY: 74342

African (AFR) AF: 0.940 AC: 38985 AN: 41488

American (AMR) AF: 0.815 AC: 12464 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2659 AN: 3470

East Asian (EAS) AF: 0.887 AC: 4586 AN: 5168

South Asian (SAS) AF: 0.921 AC: 4454 AN: 4834

European-Finnish (FIN) AF: 0.700 AC: 7387 AN: 10560

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.695 AC: 47214 AN: 67972

Other (OTH) AF: 0.790 AC: 1668 AN: 2112

Alfa AF: 0.758 Hom.: 6734

Bravo AF: 0.802

Asia WGS AF: 0.904 AC: 3142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.014
DANN	Benign	0.27
PhyloP100		-2.7
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: rs374575; hg19: chr21-40193914;