21-38814822-C-T

Position:

• chr21-38814822-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005239.6(ETS2):​c.346C>T​(p.Leu116Phe) 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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.00018 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ETS2 NM_005239.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.409

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]

ENSG00000205622 (HGNC:56712): (ETS2 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.010845423).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ETS2	NM_005239.6	c.346C>T	p.Leu116Phe	missense_variant	5/10	ENST00000360938.8	NP_005230.1
ETS2	NM_001256295.2	c.766C>T	p.Leu256Phe	missense_variant	6/11		NP_001243224.1
ETS2	XM_005260935.2	c.346C>T	p.Leu116Phe	missense_variant	5/10		XP_005260992.1
ETS2	XM_017028290.2	c.346C>T	p.Leu116Phe	missense_variant	5/10		XP_016883779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ETS2	ENST00000360938.8	c.346C>T	p.Leu116Phe	missense_variant	5/10	1	NM_005239.6	ENSP00000354194.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000179 AC: 262 AN: 1460984 Hom.: 0 Cov.: 32 AF XY: 0.000195 AC XY: 142 AN XY: 726808

Gnomad4 AFR exome AF: 0.0000597

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00387

Gnomad4 NFE exome AF: 0.0000189

Gnomad4 OTH exome AF: 0.000531

GnomAD4 genome Cov.: 33

ExAC AF: 0.0135 AC: 1642

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	23
DANN	Benign	0.90
DEOGEN2	Benign	0.33	T;T;.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.23
FATHMM_MKL	Benign	0.19	N
LIST_S2	Benign	0.70	T;.;T;T
MetaRNN	Benign	0.011	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.90	L;L;.;.
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.75	N;N;N;N
REVEL	Benign	0.13
Sift	Benign	0.66	T;T;T;T
Sift4G	Benign	0.71	T;T;T;T
Polyphen		0.0010	B;B;.;B
Vest4		0.094
MPC		0.34
ClinPred		0.0032	T
GERP RS		4.1
Varity_R		0.16
gMVP		0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs78391361; hg19: chr21-40186746;