Genetic Variant PBX2:c.1024+21G>A (chr6-32187221-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0130

Publications

45 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:

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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=-0.69).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002586.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX2	NM_002586.5	MANE Select	c.1024+21G>A		intron	N/A	NP_002577.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PBX2	ENST00000375050.6	TSL:1 MANE Select	c.1024+21G>A	intron	N/A	ENSP00000364190.3	P40425
PBX2	ENST00000478678.5	TSL:1	n.1072G>A	non_coding_transcript_exon	Exon 6 of 6
PBX2	ENST00000495300.1	TSL:3	n.274+21G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31635

AN:

151946

Hom.:

3488

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.177

AC:

43546

AN:

245892

AF XY:

0.177

show subpopulations

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 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.:

AF XY:

0.219

AC XY:

158855

AN XY:

725996

show subpopulations

African (AFR)

AF:

0.252

AC:

8419

AN:

33444

American (AMR)

AF:

0.121

AC:

5394

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

3016

AN:

26124

East Asian (EAS)

AF:

0.119

AC:

4721

AN:

39696

South Asian (SAS)

AF:

0.159

AC:

13730

AN:

86204

European-Finnish (FIN)

AF:

0.141

AC:

7353

AN:

52300

Middle Eastern (MID)

AF:

0.0910

AC:

473

AN:

5198

European-Non Finnish (NFE)

AF:

0.242

AC:

268581

AN:

1111346

Other (OTH)

AF:

0.215

AC:

12951

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

12981

25962

38943

51924

64905

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9322

18644

27966

37288

46610

<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:

0.208

AC:

31638

AN:

152066

Hom.:

3480

Cov.:

AF XY:

0.200

AC XY:

14868

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.248

AC:

10289

AN:

41458

American (AMR)

AF:

0.139

AC:

2128

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.110

AC:

381

AN:

3466

East Asian (EAS)

AF:

0.138

AC:

715

AN:

5178

South Asian (SAS)

AF:

0.183

AC:

883

AN:

4824

European-Finnish (FIN)

AF:

0.138

AC:

1457

AN:

10576

Middle Eastern (MID)

AF:

0.136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.222

AC:

15099

AN:

67970

Other (OTH)

AF:

0.191

AC:

402

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1287

2575

3862

5150

6437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<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:

0.218

Hom.:

13768

Bravo

AF:

0.212

Asia WGS

AF:

0.154

AC:

534

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

0.013

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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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