Genetic Variant PBX2:c.544-15T>C (chr6-32188171-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 NM_002586.5(PBX2):c.544-15T>C variant causes a 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 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.87

Publications

14 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=-0.89).

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 rank	MANE	Protein	UniProt
PBX2	NM_002586.5 link	c.544-15T>C		intron_variant	Intron 3 of 8	ENST00000375050.6	NP_002577.2
PBX2	XM_047418839.1 link	c.199-15T>C		intron_variant	Intron 2 of 7		XP_047274795.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
PBX2	ENST00000375050.6 link	c.544-15T>C	intron_variant	Intron 3 of 8	1	NM_002586.5	ENSP00000364190.3
PBX2	ENST00000478678.5 link	n.571-15T>C	intron_variant	Intron 3 of 5	1
PBX2	ENST00000496171.1 link	n.561-15T>C	intron_variant	Intron 1 of 3	2
PBX2	ENST00000480254.1 link	n.*109T>C	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0212

AC:

3225

AN:

152192

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0308

AC:

7419

AN:

240720

AF XY:

0.0321

show subpopulations

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 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.:

AF XY:

0.0218

AC XY:

15616

AN XY:

716648

show subpopulations

African (AFR)

AF:

0.00527

AC:

175

AN:

33184

American (AMR)

AF:

0.0219

AC:

959

AN:

43834

Ashkenazi Jewish (ASJ)

AF:

0.0590

AC:

1474

AN:

24986

East Asian (EAS)

AF:

0.0831

AC:

3278

AN:

39444

South Asian (SAS)

AF:

0.0492

AC:

4142

AN:

84258

European-Finnish (FIN)

AF:

0.0250

AC:

1320

AN:

52874

Middle Eastern (MID)

AF:

0.0418

AC:

227

AN:

5426

European-Non Finnish (NFE)

AF:

0.0151

AC:

16655

AN:

1101668

Other (OTH)

AF:

0.0277

AC:

1647

AN:

59546

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

1657

3313

4970

6626

8283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

692

1384

2076

2768

3460

<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:

0.0211

AC:

3220

AN:

152310

Hom.:

Cov.:

AF XY:

0.0229

AC XY:

1707

AN XY:

74472

show subpopulations

African (AFR)

AF:

0.00440

AC:

183

AN:

41574

American (AMR)

AF:

0.0229

AC:

350

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0625

AC:

217

AN:

3470

East Asian (EAS)

AF:

0.110

AC:

570

AN:

5182

South Asian (SAS)

AF:

0.0671

AC:

324

AN:

4832

European-Finnish (FIN)

AF:

0.0258

AC:

274

AN:

10624

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0180

AC:

1227

AN:

68010

Other (OTH)

AF:

0.0222

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

166

332

497

663

829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<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:

0.0219

Hom.:

173

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

(source)

DANN

Benign

0.50

PhyloP100

-2.9

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over