Genetic Variant PBX2:c.*1772T>C (chr6-32184610-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002586.5(PBX2):c.*1772T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 142,288 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.*1772T>C		downstream_gene	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.*1772T>C		downstream_gene	N/A	ENSP00000364190.3
	ENSG00000273333	ENST00000559458.2	TSL:2	n.*123T>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000141

AC:

AN:

142288

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000296

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

122082

Hom.:

AF XY:

0.00

AC XY:

AN XY:

61136

African (AFR)

AF:

0.00

AC:

AN:

3586

American (AMR)

AF:

0.00

AC:

AN:

3898

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

5200

East Asian (EAS)

AF:

0.00

AC:

AN:

10692

South Asian (SAS)

AF:

0.00

AC:

AN:

2264

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7310

Middle Eastern (MID)

AF:

0.00

AC:

AN:

654

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

79952

Other (OTH)

AF:

0.00

AC:

AN:

8526

GnomAD4 genome

AF:

0.0000141

AC:

AN:

142288

Hom.:

Cov.:

AF XY:

0.0000144

AC XY:

AN XY:

69530

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33570

American (AMR)

AF:

0.00

AC:

AN:

14564

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3382

East Asian (EAS)

AF:

0.00

AC:

AN:

4886

South Asian (SAS)

AF:

0.00

AC:

AN:

4614

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000296

AC:

AN:

67536

Other (OTH)

AF:

0.00

AC:

AN:

1956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

186

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

5.9

(source)

DANN

Benign

0.68

PhyloP100

0.21

PromoterAI

0.0079

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over