rs77688599

Variant names:

• chr21-38814515-G-A
• rs77688599
• NM_005239.6:c.304+123G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_005239.6(ETS2):​c.304+123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0264 in 1,217,990 control chromosomes in the GnomAD database, including 467 homozygotes. 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: 𝑓 0.021 (48 hom., cov: 33)
  • Exomes 𝑓: 0.027 (419 hom.)
• Consequence: ETS2 NM_005239.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.998

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0211 (3218/152296) while in subpopulation NFE AF= 0.0305 (2074/68022). AF 95% confidence interval is 0.0294. There are 48 homozygotes in gnomad4. There are 1539 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3218 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETS2	NM_005239.6	c.304+123G>A		intron_variant	Intron 4 of 9	ENST00000360938.8	NP_005230.1
ETS2	NM_001256295.2	c.724+123G>A		intron_variant	Intron 5 of 10		NP_001243224.1
ETS2	XM_005260935.2	c.304+123G>A		intron_variant	Intron 4 of 9		XP_005260992.1
ETS2	XM_017028290.2	c.304+123G>A		intron_variant	Intron 4 of 9		XP_016883779.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETS2	ENST00000360938.8	c.304+123G>A		intron_variant	Intron 4 of 9	1	NM_005239.6	ENSP00000354194.3

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3219 AN: 152178 Hom.: 48 Cov.: 33

Gnomad AFR AF: 0.00560

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.0231

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00683

Gnomad FIN AF: 0.0275

Gnomad MID AF: 0.0255

Gnomad NFE AF: 0.0305

Gnomad OTH AF: 0.0315

GnomAD4 exome AF: 0.0271 AC: 28923 AN: 1065694 Hom.: 419 AF XY: 0.0267 AC XY: 14211 AN XY: 533162

Gnomad4 AFR exome AF: 0.00416

Gnomad4 AMR exome AF: 0.0192

Gnomad4 ASJ exome AF: 0.0216

Gnomad4 EAS exome AF: 0.0000552

Gnomad4 SAS exome AF: 0.00673

Gnomad4 FIN exome AF: 0.0320

Gnomad4 NFE exome AF: 0.0308

Gnomad4 OTH exome AF: 0.0282

GnomAD4 genome AF: 0.0211 AC: 3218 AN: 152296 Hom.: 48 Cov.: 33 AF XY: 0.0207 AC XY: 1539 AN XY: 74476

Gnomad4 AFR AF: 0.00558

Gnomad4 AMR AF: 0.0256

Gnomad4 ASJ AF: 0.0231

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00684

Gnomad4 FIN AF: 0.0275

Gnomad4 NFE AF: 0.0305

Gnomad4 OTH AF: 0.0312

Alfa AF: 0.0271 Hom.: 10

Bravo AF: 0.0208

Asia WGS AF: 0.00462 AC: 16 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.7
DANN	Benign	0.51

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

Publications

LitVar

Other links and lift over

dbSNP: rs77688599; hg19: chr21-40186439;