Genetic Variant PBX2:c.*1772T>A (chr6-32184610-A-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.*1772T>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 264,064 control chromosomes in the GnomAD database, including 8,196 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 ( 3854 hom., cov: 33)

Exomes 𝑓: 0.25 ( 4342 hom. )

Consequence

PBX2
NM_002586.5 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.213

Publications

217 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:

ENSG00000273333 (HGNC:):

ENSG00000273333 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=-0.8).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBX2	NM_002586.5 link	c.*1772T>A		downstream_gene_variant		ENST00000375050.6	NP_002577.2
PBX2	XM_047418839.1 link	c.*1772T>A		downstream_gene_variant			XP_047274795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBX2	ENST00000375050.6 link	c.*1772T>A		downstream_gene_variant		1	NM_002586.5	ENSP00000364190.3
ENSG00000273333	ENST00000559458.2 link	n.*123T>A		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

29930

AN:

142242

Hom.:

3845

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0509

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.306

Gnomad ASJ

AF:

0.360

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.313

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.250

Gnomad OTH

AF:

0.239

GnomAD4 exome

AF:

0.252

AC:

30630

AN:

121722

Hom.:

4342

AF XY:

0.255

AC XY:

15535

AN XY:

60952

show subpopulations

African (AFR)

AF:

0.0547

AC:

196

AN:

3586

American (AMR)

AF:

0.273

AC:

1058

AN:

3882

Ashkenazi Jewish (ASJ)

AF:

0.362

AC:

1877

AN:

5186

East Asian (EAS)

AF:

0.215

AC:

2286

AN:

10654

South Asian (SAS)

AF:

0.144

AC:

324

AN:

2252

European-Finnish (FIN)

AF:

0.303

AC:

2212

AN:

7290

Middle Eastern (MID)

AF:

0.377

AC:

245

AN:

650

European-Non Finnish (NFE)

AF:

0.257

AC:

20460

AN:

79714

Other (OTH)

AF:

0.232

AC:

1972

AN:

8508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1062

2124

3185

4247

5309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

256

384

512

640

<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:

0.210

AC:

29959

AN:

142342

Hom.:

3854

Cov.:

AF XY:

0.215

AC XY:

14936

AN XY:

69610

show subpopulations

African (AFR)

AF:

0.0508

AC:

1711

AN:

33666

American (AMR)

AF:

0.307

AC:

4473

AN:

14574

Ashkenazi Jewish (ASJ)

AF:

0.360

AC:

1216

AN:

3382

East Asian (EAS)

AF:

0.148

AC:

719

AN:

4874

South Asian (SAS)

AF:

0.169

AC:

777

AN:

4608

European-Finnish (FIN)

AF:

0.313

AC:

3307

AN:

10558

Middle Eastern (MID)

AF:

0.352

AC:

102

AN:

290

European-Non Finnish (NFE)

AF:

0.250

AC:

16899

AN:

67508

Other (OTH)

AF:

0.244

AC:

483

AN:

1978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1172

2344

3515

4687

5859

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.103

Hom.:

186

Bravo

AF:

0.192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

3.6

(source)

DANN

Benign

0.78

PhyloP100

0.21

PromoterAI

-0.048

Neutral

(source)

Splicing

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