rs204994

chr6-32187221-C-T

Variant summary

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

The NM_002586.5(PBX2):c.1024+21G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,611,374 control chromosomes in the GnomAD database, including 42,070 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 0.21 (3480 hom., cov: 32)
  • Exomes 𝑓: 0.22 (38590 hom.)
• Consequence: PBX2 NM_002586.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130

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=-0.69).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBX2	NM_002586.5	c.1024+21G>A		intron_variant		ENST00000375050.6
PBX2	XM_047418839.1	c.679+21G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBX2	ENST00000375050.6	c.1024+21G>A		intron_variant		1	NM_002586.5	P1
PBX2	ENST00000478678.5	n.1072G>A		non_coding_transcript_exon_variant	6/6	1
PBX2	ENST00000495300.1	n.274+21G>A		intron_variant, non_coding_transcript_variant		3
PBX2	ENST00000496171.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.208 AC: 31635 AN: 151946 Hom.: 3488 Cov.: 32

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.191

GnomAD3 exomes AF: 0.177 AC: 43546 AN: 245892 Hom.: 4319 AF XY: 0.177 AC XY: 23771 AN XY: 134046

Gnomad AFR exome AF: 0.259

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.154

Gnomad SAS exome AF: 0.159

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.209

Gnomad OTH exome AF: 0.176

GnomAD4 exome AF: 0.222 AC: 324638 AN: 1459308 Hom.: 38590 Cov.: 33 AF XY: 0.219 AC XY: 158855 AN XY: 725996

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.121

Gnomad4 ASJ exome AF: 0.115

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.159

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.208 AC: 31638 AN: 152066 Hom.: 3480 Cov.: 32 AF XY: 0.200 AC XY: 14868 AN XY: 74350

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.110

Gnomad4 EAS AF: 0.138

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.191

Alfa AF: 0.213 Hom.: 5461

Bravo AF: 0.212

Asia WGS AF: 0.154 AC: 534 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	11
Dann	Benign	0.75
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: rs204994; hg19: chr6-32154998; COSMIC: COSV66709134; COSMIC: COSV66709134;