rs204993

Positions:

• chr6-32187804-A-G
• chr6-32187804-A-T

Variant summary

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

The NM_002586.5(PBX2):​c.735-22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.284 in 1,609,792 control chromosomes in the GnomAD database, including 68,750 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 0.26 (5428 hom., cov: 31)
  • Exomes 𝑓: 0.29 (63322 hom.)
• Consequence: PBX2 NM_002586.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230

Genes affected

PBX2 (HGNC:8633): (PBX homeobox 2) This gene encodes a ubiquitously expressed member of the TALE/PBX homeobox family. It was identified by its similarity to a homeobox gene which is involved in t(1;19) translocation in acute pre-B-cell leukemias. This protein is a transcriptional activator which binds to the TLX1 promoter. The gene is located within the major histocompatibility complex (MHC) on chromosome 6. [provided by RefSeq, Jul 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 (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PBX2	NM_002586.5	c.735-22T>C		intron_variant		ENST00000375050.6	NP_002577.2
PBX2	XM_047418839.1	c.390-22T>C		intron_variant			XP_047274795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PBX2	ENST00000375050.6	c.735-22T>C		intron_variant		1	NM_002586.5	ENSP00000364190	P1
PBX2	ENST00000478678.5	n.762-22T>C		intron_variant, non_coding_transcript_variant		1
PBX2	ENST00000496171.1	n.752-22T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39550 AN: 151952 Hom.: 5432 Cov.: 31

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.311

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.269

Gnomad OTH AF: 0.228

GnomAD3 exomes AF: 0.238 AC: 57635 AN: 241962 Hom.: 7524 AF XY: 0.237 AC XY: 31282 AN XY: 131814

Gnomad AFR exome AF: 0.302

Gnomad AMR exome AF: 0.152

Gnomad ASJ exome AF: 0.168

Gnomad EAS exome AF: 0.391

Gnomad SAS exome AF: 0.227

Gnomad FIN exome AF: 0.162

Gnomad NFE exome AF: 0.256

Gnomad OTH exome AF: 0.230

GnomAD4 exome AF: 0.287 AC: 417995 AN: 1457722 Hom.: 63322 Cov.: 36 AF XY: 0.283 AC XY: 204930 AN XY: 724926

Gnomad4 AFR exome AF: 0.297

Gnomad4 AMR exome AF: 0.157

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.411

Gnomad4 SAS exome AF: 0.229

Gnomad4 FIN exome AF: 0.168

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.285

GnomAD4 genome AF: 0.260 AC: 39557 AN: 152070 Hom.: 5428 Cov.: 31 AF XY: 0.253 AC XY: 18806 AN XY: 74350

Gnomad4 AFR AF: 0.293

Gnomad4 AMR AF: 0.168

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.405

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.269

Gnomad4 OTH AF: 0.228

Alfa AF: 0.265 Hom.: 10478

Bravo AF: 0.265

Asia WGS AF: 0.301 AC: 1047 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	0.57
DANN	Benign	0.34

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: rs204993; hg19: chr6-32155581; COSMIC: COSV66708914; COSMIC: COSV66708914;