21-38819507-T-C

Variant names:

• chr21-38819507-T-C
• NM_005239.6:c.816T>C
• ETS2 p.Thr272Thr

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_005239.6(ETS2):​c.816T>C​(p.Thr272Thr) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ETS2 NM_005239.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0880
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=-0.088 with no splicing effect.

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.816T>C	p.Thr272Thr	synonymous	Exon 8 of 10	NP_005230.1	P15036
	ETS2	NM_001256295.2		c.1236T>C	p.Thr412Thr	synonymous	Exon 9 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.816T>C	p.Thr272Thr	synonymous	Exon 8 of 10	ENSP00000354194.3	P15036
	ETS2	ENST00000667466.1		c.816T>C	p.Thr272Thr	synonymous	Exon 8 of 10	ENSP00000499540.1	A0A590UJP9
	ETS2	ENST00000968691.1		c.840T>C	p.Thr280Thr	synonymous	Exon 8 of 10	ENSP00000638750.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.70
PhyloP100		-0.088

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr21-40191431;