rs2071292

Positions:

• chr6-32188171-A-G

Variant summary

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

The NM_002586.5(PBX2):​c.544-15T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0207 in 1,597,530 control chromosomes in the GnomAD database, including 704 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 0.021 (92 hom., cov: 32)
  • Exomes 𝑓: 0.021 (612 hom.)
• Consequence: PBX2 NM_002586.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.87

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBX2	NM_002586.5	c.544-15T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000375050.6
PBX2	XM_047418839.1	c.199-15T>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBX2	ENST00000375050.6	c.544-15T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_002586.5	P1
PBX2	ENST00000478678.5	n.571-15T>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		1
PBX2	ENST00000496171.1	n.561-15T>C		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3225 AN: 152192 Hom.: 93 Cov.: 32

Gnomad AFR AF: 0.00439

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0229

Gnomad ASJ AF: 0.0625

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0668

Gnomad FIN AF: 0.0258

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.0229

GnomAD3 exomes AF: 0.0308 AC: 7419 AN: 240720 Hom.: 245 AF XY: 0.0321 AC XY: 4165 AN XY: 129626

Gnomad AFR exome AF: 0.00365

Gnomad AMR exome AF: 0.0201

Gnomad ASJ exome AF: 0.0600

Gnomad EAS exome AF: 0.116

Gnomad SAS exome AF: 0.0466

Gnomad FIN exome AF: 0.0273

Gnomad NFE exome AF: 0.0183

Gnomad OTH exome AF: 0.0248

GnomAD4 exome AF: 0.0207 AC: 29877 AN: 1445220 Hom.: 612 Cov.: 33 AF XY: 0.0218 AC XY: 15616 AN XY: 716648

Gnomad4 AFR exome AF: 0.00527

Gnomad4 AMR exome AF: 0.0219

Gnomad4 ASJ exome AF: 0.0590

Gnomad4 EAS exome AF: 0.0831

Gnomad4 SAS exome AF: 0.0492

Gnomad4 FIN exome AF: 0.0250

Gnomad4 NFE exome AF: 0.0151

Gnomad4 OTH exome AF: 0.0277

GnomAD4 genome AF: 0.0211 AC: 3220 AN: 152310 Hom.: 92 Cov.: 32 AF XY: 0.0229 AC XY: 1707 AN XY: 74472

Gnomad4 AFR AF: 0.00440

Gnomad4 AMR AF: 0.0229

Gnomad4 ASJ AF: 0.0625

Gnomad4 EAS AF: 0.110

Gnomad4 SAS AF: 0.0671

Gnomad4 FIN AF: 0.0258

Gnomad4 NFE AF: 0.0180

Gnomad4 OTH AF: 0.0222

Alfa AF: 0.0238 Hom.: 105

Bravo AF: 0.0190

Asia WGS AF: 0.0550 AC: 192 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.86
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2071292; hg19: chr6-32155948;