rs1803557

chr21-38814910-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005239.6(ETS2):c.434A>T(p.Glu145Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ETS2 NM_005239.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.21

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ETS2	NM_005239.6	c.434A>T	p.Glu145Val	missense_variant	5/10	ENST00000360938.8
ETS2	NM_001256295.2	c.854A>T	p.Glu285Val	missense_variant	6/11
ETS2	XM_005260935.2	c.434A>T	p.Glu145Val	missense_variant	5/10
ETS2	XM_017028290.2	c.434A>T	p.Glu145Val	missense_variant	5/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ETS2	ENST00000360938.8	c.434A>T	p.Glu145Val	missense_variant	5/10	1	NM_005239.6	P1
ETS2-AS1	ENST00000663561.1	n.535-1485T>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
Cadd	Pathogenic	35
Dann	Uncertain	0.99
DEOGEN2	Uncertain	0.50	D;D;.;T
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.78
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;.;D;D
M_CAP	Benign	0.050	D
MetaRNN	Uncertain	0.72	D;D;D;D
MetaSVM	Benign	-0.59	T
MutationAssessor	Uncertain	2.5	M;M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.8	D;D;D;D
REVEL	Uncertain	0.39
Sift	Uncertain	0.026	D;D;D;D
Sift4G	Benign	0.10	T;T;D;D
Polyphen		1.0	D;D;.;D
Vest4		0.74
MutPred		0.52		Loss of ubiquitination at K144 (P = 0.057);Loss of ubiquitination at K144 (P = 0.057);Loss of ubiquitination at K144 (P = 0.057);Loss of ubiquitination at K144 (P = 0.057);
MVP		0.62
MPC		1.1
ClinPred		0.99	D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.61
gMVP		0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.97		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.97		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1803557; hg19: chr21-40186834;