Genetic Variant PBX2:c.735-22T>C (chr6-32187804-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000375050.6(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
ENST00000375050.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.230

Publications

104 publications found

Variant links:

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]

PBX2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000375050.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX2	NM_002586.5	MANE Select	c.735-22T>C		intron	N/A	NP_002577.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
PBX2	ENST00000375050.6	TSL:1 MANE Select	c.735-22T>C	intron	N/A	ENSP00000364190.3
PBX2	ENST00000478678.5	TSL:1	n.762-22T>C	intron	N/A
PBX2	ENST00000496171.1	TSL:2	n.752-22T>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.260

AC:

39550

AN:

151952

Hom.:

5432

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.238

AC:

57635

AN:

241962

AF XY:

0.237

show subpopulations

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 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.:

AF XY:

0.283

AC XY:

204930

AN XY:

724926

show subpopulations

African (AFR)

AF:

0.297

AC:

9916

AN:

33442

American (AMR)

AF:

0.157

AC:

6968

AN:

44444

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

4487

AN:

26002

East Asian (EAS)

AF:

0.411

AC:

16298

AN:

39654

South Asian (SAS)

AF:

0.229

AC:

19634

AN:

85754

European-Finnish (FIN)

AF:

0.168

AC:

8750

AN:

52160

Middle Eastern (MID)

AF:

0.138

AC:

798

AN:

5762

European-Non Finnish (NFE)

AF:

0.301

AC:

333977

AN:

1110206

Other (OTH)

AF:

0.285

AC:

17167

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

14875

29751

44626

59502

74377

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11386

22772

34158

45544

56930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.260

AC:

39557

AN:

152070

Hom.:

5428

Cov.:

AF XY:

0.253

AC XY:

18806

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.293

AC:

12151

AN:

41428

American (AMR)

AF:

0.168

AC:

2561

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

568

AN:

3466

East Asian (EAS)

AF:

0.405

AC:

2088

AN:

5160

South Asian (SAS)

AF:

0.272

AC:

1309

AN:

4816

European-Finnish (FIN)

AF:

0.165

AC:

1747

AN:

10606

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.269

AC:

18320

AN:

67990

Other (OTH)

AF:

0.228

AC:

482

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1510

3020

4530

6040

7550

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.268

Hom.:

25000

Bravo

AF:

0.265

Asia WGS

AF:

0.301

AC:

1047

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.57

(source)

DANN

Benign

0.34

PhyloP100

-0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over