21-38814371-C-T

Variant names:

• chr21-38814371-C-T
• rs760122401
• NM_005239.6:c.283C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_005239.6(ETS2):​c.283C>T​(p.Arg95Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000223 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R95Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: ETS2 NM_005239.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.67
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.20721805).
• BS2: High AC in GnomAd4 at 5 AD gene.

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.283C>T	p.Arg95Trp	missense	Exon 4 of 10	NP_005230.1	P15036
	ETS2	NM_001256295.2		c.703C>T	p.Arg235Trp	missense	Exon 5 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.283C>T	p.Arg95Trp	missense	Exon 4 of 10	ENSP00000354194.3	P15036
	ETS2	ENST00000667466.1		c.283C>T	p.Arg95Trp	missense	Exon 4 of 10	ENSP00000499540.1	A0A590UJP9
	ETS2	ENST00000968691.1		c.283C>T	p.Arg95Trp	missense	Exon 4 of 10	ENSP00000638750.1

Frequencies

GnomAD3 genomes AF: 0.0000328 AC: 5 AN: 152216 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000358 AC: 9 AN: 251330 AF XY: 0.0000221

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461760 Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12 AN XY: 727176

African (AFR) AF: 0.0000597 AC: 2 AN: 33474

American (AMR) AF: 0.000112 AC: 5 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53336

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1111986

Other (OTH) AF: 0.0000497 AC: 3 AN: 60392

GnomAD4 genome AF: 0.0000328 AC: 5 AN: 152216 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74350

African (AFR) AF: 0.0000241 AC: 1 AN: 41460

American (AMR) AF: 0.000196 AC: 3 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68044

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.0000658 Hom.: 0

Bravo AF: 0.0000793

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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	0.13
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.51	D
Eigen	Benign	-0.031
Eigen_PC	Benign	-0.078
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		1.7
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.23
Sift	Benign	0.060	T
Sift4G	Uncertain	0.036	D
Polyphen		1.0	D
Vest4		0.41
MVP		0.50
MPC		0.96
ClinPred		0.18	T
GERP RS		2.9
Varity_R		0.14
gMVP		0.45
Mutation Taster		=80/20	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

dbSNP: rs760122401; hg19: chr21-40186295;