Genetic Variant PBX2:c.1201-34T>C (chr6-32186508-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.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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.413

Publications

53 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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.38 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.1201-34T>C		intron	N/A	NP_002577.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX2	ENST00000375050.6	TSL:1 MANE Select	c.1201-34T>C		intron	N/A	ENSP00000364190.3
	PBX2	ENST00000495300.1	TSL:3	n.668T>C		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.263

AC:

39925

AN:

151890

Hom.:

5781

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.211

AC:

52956

AN:

250398

AF XY:

0.211

show subpopulations

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 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.:

AF XY:

0.240

AC XY:

172748

AN XY:

720888

show subpopulations

African (AFR)

AF:

0.393

AC:

13044

AN:

33192

American (AMR)

AF:

0.150

AC:

6718

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.155

AC:

4043

AN:

26044

East Asian (EAS)

AF:

0.251

AC:

9960

AN:

39604

South Asian (SAS)

AF:

0.209

AC:

18002

AN:

85944

European-Finnish (FIN)

AF:

0.141

AC:

7529

AN:

53216

Middle Eastern (MID)

AF:

0.152

AC:

872

AN:

5726

European-Non Finnish (NFE)

AF:

0.251

AC:

275929

AN:

1098718

Other (OTH)

AF:

0.251

AC:

15003

AN:

59890

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

14517

29034

43551

58068

72585

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9606

19212

28818

38424

48030

<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:

0.263

AC:

39935

AN:

152010

Hom.:

5774

Cov.:

AF XY:

0.255

AC XY:

18977

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.385

AC:

15933

AN:

41404

American (AMR)

AF:

0.192

AC:

2930

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

509

AN:

3468

East Asian (EAS)

AF:

0.241

AC:

1249

AN:

5176

South Asian (SAS)

AF:

0.235

AC:

1130

AN:

4808

European-Finnish (FIN)

AF:

0.139

AC:

1474

AN:

10602

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.234

AC:

15889

AN:

67952

Other (OTH)

AF:

0.248

AC:

522

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1475

2950

4424

5899

7374

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

406

812

1218

1624

2030

<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:

0.243

Hom.:

19060

Bravo

AF:

0.275

Asia WGS

AF:

0.251

AC:

873

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.3

(source)

DANN

Benign

0.65

PhyloP100

0.41

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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