rs2239839

Positions:

• chr6-33320298-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001141969.2(DAXX):​c.1252-74G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.286 in 1,424,010 control chromosomes in the GnomAD database, including 62,287 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 0.24 (5335 hom., cov: 32)
  • Exomes 𝑓: 0.29 (56952 hom.)
• Consequence: DAXX NM_001141969.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.644

Genes affected

DAXX (HGNC:2681): (death domain associated protein) This gene encodes a multifunctional protein that resides in multiple locations in the nucleus and in the cytoplasm. It interacts with a wide variety of proteins, such as apoptosis antigen Fas, centromere protein C, and transcription factor erythroblastosis virus E26 oncogene homolog 1. In the nucleus, the encoded protein functions as a potent transcription repressor that binds to sumoylated transcription factors. Its repression can be relieved by the sequestration of this protein into promyelocytic leukemia nuclear bodies or nucleoli. This protein also associates with centromeres in G2 phase. In the cytoplasm, the encoded protein may function to regulate apoptosis. The subcellular localization and function of this protein are modulated by post-translational modifications, including sumoylation, phosphorylation and polyubiquitination. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

DAXX (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DAXX	NM_001141969.2	c.1252-74G>T		intron_variant		ENST00000374542.10	NP_001135441.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAXX	ENST00000374542.10	c.1252-74G>T		intron_variant		1	NM_001141969.2	ENSP00000363668.5

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35845 AN: 151964 Hom.: 5342 Cov.: 32

Gnomad AFR AF: 0.0547

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.306

Gnomad OTH AF: 0.202

GnomAD3 exomes AF: 0.298 AC: 74108 AN: 248772 Hom.: 11952 AF XY: 0.302 AC XY: 40737 AN XY: 134668

Gnomad AFR exome AF: 0.0515

Gnomad AMR exome AF: 0.365

Gnomad ASJ exome AF: 0.222

Gnomad EAS exome AF: 0.252

Gnomad SAS exome AF: 0.310

Gnomad FIN exome AF: 0.371

Gnomad NFE exome AF: 0.311

Gnomad OTH exome AF: 0.287

GnomAD4 exome AF: 0.292 AC: 370916 AN: 1271928 Hom.: 56952 Cov.: 19 AF XY: 0.294 AC XY: 188881 AN XY: 642196

Gnomad4 AFR exome AF: 0.0448

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.259

Gnomad4 SAS exome AF: 0.313

Gnomad4 FIN exome AF: 0.368

Gnomad4 NFE exome AF: 0.296

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.236 AC: 35842 AN: 152082 Hom.: 5335 Cov.: 32 AF XY: 0.241 AC XY: 17938 AN XY: 74320

Gnomad4 AFR AF: 0.0545

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.227

Gnomad4 EAS AF: 0.257

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.368

Gnomad4 NFE AF: 0.306

Gnomad4 OTH AF: 0.200

Alfa AF: 0.290 Hom.: 11409

Bravo AF: 0.219

Asia WGS AF: 0.233 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2239839; hg19: chr6-33288075; COSMIC: COSV56467676; COSMIC: COSV56467676;