dbSNP rs1800625: PBX2:c.*1717T>C (chr6-32184665-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.*1717T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 207,222 control chromosomes in the GnomAD database, including 2,516 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 0.15 ( 1731 hom., cov: 33)

Exomes 𝑓: 0.15 ( 785 hom. )

Consequence

PBX2
NM_002586.5 downstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0380

Publications

225 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=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBX2	NM_002586.5 link	c.*1717T>C		downstream_gene_variant		ENST00000375050.6	NP_002577.2	P40425A0A024RCR3
PBX2	XM_047418839.1 link	c.*1717T>C		downstream_gene_variant			XP_047274795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBX2	ENST00000375050.6 link	c.*1717T>C		downstream_gene_variant		1	NM_002586.5	ENSP00000364190.3		P40425
ENSG00000273333	ENST00000559458.2 link	n.*68T>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.146

AC:

21856

AN:

150010

Hom.:

1736

Cov.:

show subpopulations

Gnomad AFR

AF:

0.121

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.0828

Gnomad ASJ

AF:

0.0876

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.157

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.180

Gnomad OTH

AF:

0.129

GnomAD4 exome

AF:

0.149

AC:

8525

AN:

57098

Hom.:

785

AF XY:

0.151

AC XY:

4320

AN XY:

28580

show subpopulations

African (AFR)

AF:

0.0998

AC:

222

AN:

2224

American (AMR)

AF:

0.0746

AC:

123

AN:

1648

Ashkenazi Jewish (ASJ)

AF:

0.0919

AC:

237

AN:

2578

East Asian (EAS)

AF:

0.0931

AC:

459

AN:

4928

South Asian (SAS)

AF:

0.147

AC:

AN:

470

European-Finnish (FIN)

AF:

0.128

AC:

351

AN:

2746

Middle Eastern (MID)

AF:

0.0851

AC:

AN:

376

European-Non Finnish (NFE)

AF:

0.169

AC:

6412

AN:

38018

Other (OTH)

AF:

0.151

AC:

620

AN:

4110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

338

676

1015

1353

1691

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.146

AC:

21846

AN:

150124

Hom.:

1731

Cov.:

AF XY:

0.141

AC XY:

10358

AN XY:

73390

show subpopulations

African (AFR)

AF:

0.121

AC:

4812

AN:

39860

American (AMR)

AF:

0.0824

AC:

1244

AN:

15090

Ashkenazi Jewish (ASJ)

AF:

0.0876

AC:

303

AN:

3460

East Asian (EAS)

AF:

0.105

AC:

538

AN:

5136

South Asian (SAS)

AF:

0.156

AC:

746

AN:

4794

European-Finnish (FIN)

AF:

0.137

AC:

1453

AN:

10584

Middle Eastern (MID)

AF:

0.0884

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.180

AC:

12244

AN:

67912

Other (OTH)

AF:

0.129

AC:

269

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

985

1969

2954

3938

4923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.178

Hom.:

3250

Bravo

AF:

0.140

Asia WGS

AF:

0.113

AC:

392

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.0

(source)

DANN

Benign

0.56

PhyloP100

-0.038

PromoterAI

-0.0059

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