NM_005239.6:c.1195-248A>G

Variant names:

• chr21-38822426-A-G
• rs7276961
• NM_005239.6:c.1195-248A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 (EAS) allele frequency at 95% confidence interval = 0.4 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS2	NM_005239.6	c.1195-248A>G		intron_variant	Intron 9 of 9	ENST00000360938.8	NP_005230.1
ETS2	NM_001256295.2	c.1615-248A>G		intron_variant	Intron 10 of 10		NP_001243224.1
ETS2	XM_005260935.2	c.1195-248A>G		intron_variant	Intron 9 of 9		XP_005260992.1
ETS2	XM_017028290.2	c.1195-248A>G		intron_variant	Intron 9 of 9		XP_016883779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETS2	ENST00000360938.8	c.1195-248A>G		intron_variant	Intron 9 of 9	1	NM_005239.6	ENSP00000354194.3

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

African (AFR) AF: 0.405 AC: 16780 AN: 41416

American (AMR) AF: 0.364 AC: 5559 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1170 AN: 3470

East Asian (EAS) AF: 0.411 AC: 2115 AN: 5148

South Asian (SAS) AF: 0.357 AC: 1718 AN: 4806

European-Finnish (FIN) AF: 0.369 AC: 3896 AN: 10546

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24688 AN: 67950

Other (OTH) AF: 0.356 AC: 752 AN: 2112

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
PhyloP100		-0.49
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: rs7276961; hg19: chr21-40194350;