rs7276961

chr21-38822426-A-Gchr21-38822426-A-C

Variant summary

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

The NM_005239.6(ETS2):c.1195-248A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.376 in 151,930 control chromosomes in the GnomAD database, including 10,905 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 0.38 (10905 hom., cov: 32)
• Consequence: ETS2 NM_005239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETS2	NM_005239.6	c.1195-248A>G		intron_variant		ENST00000360938.8
ETS2	NM_001256295.2	c.1615-248A>G		intron_variant
ETS2	XM_005260935.2	c.1195-248A>G		intron_variant
ETS2	XM_017028290.2	c.1195-248A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETS2	ENST00000360938.8	c.1195-248A>G		intron_variant		1	NM_005239.6	P1
ETS2-AS1	ENST00000663561.1	n.535-9001T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57110 AN: 151810 Hom.: 10892 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.426

Gnomad AMR AF: 0.364

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.356

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

GnomAD4 genome AF: 0.376 AC: 57158 AN: 151930 Hom.: 10905 Cov.: 32 AF XY: 0.375 AC XY: 27828 AN XY: 74250

Gnomad4 AFR AF: 0.405

Gnomad4 AMR AF: 0.364

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.357

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.356

Alfa AF: 0.235 Hom.: 568

Bravo AF: 0.375

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.2
Dann	Benign	0.68

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: rs7276961; hg19: chr21-40194350;