Genetic Variant NM_002586.5: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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX2	NM_002586.5	MANE Select	c.544-15T>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.544-15T>C	intron	N/A	ENSP00000364190.3
PBX2	ENST00000478678.5	TSL:1	n.571-15T>C	intron	N/A
PBX2	ENST00000496171.1	TSL:2	n.561-15T>C	intron	N/A

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over