rs2073525

Positions:

• chr6-33323048-A-G

Variant summary

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

The XR_007059547.1(LOC124901303):​n.185A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 508,108 control chromosomes in the GnomAD database, including 83,303 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 0.59 (27359 hom., cov: 33)
  • Exomes 𝑓: 0.55 (55944 hom.)
• Consequence: LOC124901303 XR_007059547.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.54

Genes affected

LOC124901303 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124901303	XR_007059547.1	n.185A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DAXX	ENST00000266000.10			upstream_gene_variant		1		ENSP00000266000	P2
DAXX	ENST00000414083.6			upstream_gene_variant		2		ENSP00000396876
DAXX	ENST00000620164.4			upstream_gene_variant		5		ENSP00000482399
DAXX	ENST00000706094.1			upstream_gene_variant				ENSP00000516212	A2

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89929 AN: 152020 Hom.: 27313 Cov.: 33

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.576

Gnomad ASJ AF: 0.577

Gnomad EAS AF: 0.421

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.567

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.583

GnomAD4 exome AF: 0.555 AC: 197544 AN: 355970 Hom.: 55944 Cov.: 4 AF XY: 0.563 AC XY: 107169 AN XY: 190268

Gnomad4 AFR exome AF: 0.737

Gnomad4 AMR exome AF: 0.551

Gnomad4 ASJ exome AF: 0.574

Gnomad4 EAS exome AF: 0.393

Gnomad4 SAS exome AF: 0.658

Gnomad4 FIN exome AF: 0.526

Gnomad4 NFE exome AF: 0.533

Gnomad4 OTH exome AF: 0.567

GnomAD4 genome AF: 0.592 AC: 90028 AN: 152138 Hom.: 27359 Cov.: 33 AF XY: 0.592 AC XY: 44045 AN XY: 74342

Gnomad4 AFR AF: 0.737

Gnomad4 AMR AF: 0.576

Gnomad4 ASJ AF: 0.577

Gnomad4 EAS AF: 0.420

Gnomad4 SAS AF: 0.652

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.581

Alfa AF: 0.549 Hom.: 13000

Bravo AF: 0.599

Asia WGS AF: 0.533 AC: 1855 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.56
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2073525; hg19: chr6-33290825; COSMIC: COSV56467678;