Genetic Variant PBX2:p.Ser67Asn (chr6-32189716-C-T) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4BS2

The NM_002586.5(PBX2):c.200G>A(p.Ser67Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,457,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PBX2
NM_002586.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

Publications

0 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: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38623655).

BS2

High AC in GnomAdExome4 at 5 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX2	NM_002586.5	MANE Select	c.200G>A	p.Ser67Asn	missense	Exon 1 of 9	NP_002577.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX2	ENST00000375050.6	TSL:1 MANE Select	c.200G>A	p.Ser67Asn	missense	Exon 1 of 9	ENSP00000364190.3	P40425
	PBX2	ENST00000478678.5	TSL:1	n.227G>A		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000288

AC:

AN:

243226

AF XY:

0.0000301

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1457658

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725228

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33138

American (AMR)

AF:

0.000112

AC:

AN:

44584

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25964

East Asian (EAS)

AF:

0.00

AC:

AN:

39172

South Asian (SAS)

AF:

0.00

AC:

AN:

86158

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110270

Other (OTH)

AF:

0.00

AC:

AN:

60246

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.435

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000166

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.47

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.79

M_CAP

Benign

0.038

MetaRNN

Benign

0.39

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.8

PhyloP100

4.0

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

-2.2

REVEL

Benign

0.17

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.016

Polyphen

1.0

Vest4

0.49

MutPred

0.58

Gain of relative solvent accessibility (P = 0.0215)

MVP

0.68

MPC

1.3

ClinPred

0.75

GERP RS

4.0

PromoterAI

0.00020

Neutral

(source)

Varity_R

0.17

gMVP

0.53

Mutation Taster

=55/45

polymorphism

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over