chr21-38818515-C-G

Variant names:

• chr21-38818515-C-G
• NM_005239.6:c.680C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005239.6(ETS2):​c.680C>G​(p.Pro227Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ETS2 NM_005239.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.51
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12872723).

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.680C>G	p.Pro227Arg	missense	Exon 7 of 10	NP_005230.1	P15036
	ETS2	NM_001256295.2		c.1100C>G	p.Pro367Arg	missense	Exon 8 of 11	NP_001243224.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ETS2	ENST00000360938.8	TSL:1 MANE Select	c.680C>G	p.Pro227Arg	missense	Exon 7 of 10	ENSP00000354194.3	P15036
	ETS2	ENST00000667466.1		c.680C>G	p.Pro227Arg	missense	Exon 7 of 10	ENSP00000499540.1	A0A590UJP9
	ETS2	ENST00000968691.1		c.680C>G	p.Pro227Arg	missense	Exon 7 of 10	ENSP00000638750.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.50	D
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0090	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		3.5
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.18
Sift	Benign	0.032	D
Sift4G	Benign	0.35	T
Polyphen		0.10	B
Vest4		0.61
MutPred		0.18		Gain of catalytic residue at P227 (P = 0.0353)
MVP		0.37
MPC		0.44
ClinPred		0.24	T
GERP RS		6.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.056
gMVP		0.63
Mutation Taster		=92/8	polymorphism

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

hg19: chr21-40190439;