rs34472454

Variant names:

• chr21-38814971-A-AC
• rs34472454
• NM_005239.6:c.495_496insC

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005239.6(ETS2):​c.495_496insC​(p.Met166HisfsTer14) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ETS2 NM_005239.6 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.63
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS2	NM_005239.6	c.495_496insC	p.Met166HisfsTer14	frameshift_variant	Exon 5 of 10	ENST00000360938.8	NP_005230.1
ETS2	NM_001256295.2	c.915_916insC	p.Met306HisfsTer14	frameshift_variant	Exon 6 of 11		NP_001243224.1
ETS2	XM_005260935.2	c.495_496insC	p.Met166HisfsTer14	frameshift_variant	Exon 5 of 10		XP_005260992.1
ETS2	XM_017028290.2	c.495_496insC	p.Met166HisfsTer14	frameshift_variant	Exon 5 of 10		XP_016883779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETS2	ENST00000360938.8	c.495_496insC	p.Met166HisfsTer14	frameshift_variant	Exon 5 of 10	1	NM_005239.6	ENSP00000354194.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6

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: rs34472454; hg19: chr21-40186895;