rs2856329

Variant names:

• chr12-11789786-C-T
• rs2856329
• NM_001987.5:c.163+37207C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001987.5(ETV6):​c.163+37207C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,976 control chromosomes in the GnomAD database, including 11,498 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 0.37 (11498 hom., cov: 32)
• Consequence: ETV6 NM_001987.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606
• Publications: 4 publications found

Genes affected

ETV6 (HGNC:3495): (ETS variant transcription factor 6) This gene encodes an ETS family transcription factor. The product of this gene contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. Gene knockout studies in mice suggest that it is required for hematopoiesis and maintenance of the developing vascular network. This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. [provided by RefSeq, Sep 2008]

ETV6 Gene-Disease associations (from GenCC):

• thrombocytopenia 5

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• acute myeloid leukemia

  Inheritance: AD, Unknown Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Ambry Genetics
• hereditary thrombocytopenia and hematologic cancer predisposition syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ETV6	NM_001987.5	c.163+37207C>T		intron_variant	Intron 2 of 7	ENST00000396373.9	NP_001978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ETV6	ENST00000396373.9	c.163+37207C>T		intron_variant	Intron 2 of 7	1	NM_001987.5	ENSP00000379658.3
ETV6	ENST00000545027.1	c.79+37207C>T		intron_variant	Intron 1 of 2	5		ENSP00000441463.1
ETV6	ENST00000541426.1	n.348-35858C>T		intron_variant	Intron 2 of 3	4

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56452 AN: 151856 Hom.: 11477 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.438

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.281

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.380

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.372 AC: 56537 AN: 151976 Hom.: 11498 Cov.: 32 AF XY: 0.369 AC XY: 27446 AN XY: 74298

African (AFR) AF: 0.528 AC: 21851 AN: 41422

American (AMR) AF: 0.468 AC: 7156 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1309 AN: 3470

East Asian (EAS) AF: 0.136 AC: 701 AN: 5168

South Asian (SAS) AF: 0.249 AC: 1201 AN: 4830

European-Finnish (FIN) AF: 0.281 AC: 2965 AN: 10554

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20048 AN: 67942

Other (OTH) AF: 0.379 AC: 799 AN: 2110

Alfa AF: 0.333 Hom.: 12462

Bravo AF: 0.395

Asia WGS AF: 0.216 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.48
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism (auto)

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: rs2856329; hg19: chr12-11942720;