rs204995

Positions:

• chr6-32186508-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.1201-34T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 1,599,042 control chromosomes in the GnomAD database, including 50,717 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 (5774 hom., cov: 31)
  • Exomes 𝑓: 0.24 (44943 hom.)
• Consequence: PBX2 NM_002586.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.413

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBX2	NM_002586.5	c.1201-34T>C		intron_variant		ENST00000375050.6
PBX2	XM_047418839.1	c.856-34T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBX2	ENST00000375050.6	c.1201-34T>C		intron_variant		1	NM_002586.5	P1
PBX2	ENST00000495300.1	n.668T>C		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39925 AN: 151890 Hom.: 5781 Cov.: 31

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.234

Gnomad OTH AF: 0.248

GnomAD3 exomes AF: 0.211 AC: 52956 AN: 250398 Hom.: 6332 AF XY: 0.211 AC XY: 28568 AN XY: 135516

Gnomad AFR exome AF: 0.397

Gnomad AMR exome AF: 0.141

Gnomad ASJ exome AF: 0.149

Gnomad EAS exome AF: 0.244

Gnomad SAS exome AF: 0.214

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.221

Gnomad OTH exome AF: 0.208

GnomAD4 exome AF: 0.243 AC: 351100 AN: 1447032 Hom.: 44943 Cov.: 27 AF XY: 0.240 AC XY: 172748 AN XY: 720888

Gnomad4 AFR exome AF: 0.393

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.251

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.141

Gnomad4 NFE exome AF: 0.251

Gnomad4 OTH exome AF: 0.251

GnomAD4 genome AF: 0.263 AC: 39935 AN: 152010 Hom.: 5774 Cov.: 31 AF XY: 0.255 AC XY: 18977 AN XY: 74322

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.192

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.234

Gnomad4 OTH AF: 0.248

Alfa AF: 0.234 Hom.: 7662

Bravo AF: 0.275

Asia WGS AF: 0.251 AC: 873 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	1.3
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs204995; hg19: chr6-32154285; COSMIC: COSV66708861; COSMIC: COSV66708861;