6-32189795-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_002586.5(PBX2):c.121A>G(p.Ser41Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,599,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PBX2
NM_002586.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.28

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.086960614).

BP6

Variant 6-32189795-T-C is Benign according to our data. Variant chr6-32189795-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2285086.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PBX2	NM_002586.5 linkuse as main transcript	c.121A>G	p.Ser41Gly	missense_variant	1/9	ENST00000375050.6
PBX2	XM_047418839.1 linkuse as main transcript	c.-151A>G		5_prime_UTR_variant	1/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PBX2	ENST00000375050.6 linkuse as main transcript	c.121A>G	p.Ser41Gly	missense_variant	1/9	1	NM_002586.5	P1
PBX2	ENST00000478678.5 linkuse as main transcript	n.148A>G		non_coding_transcript_exon_variant	1/6	1

Frequencies

GnomAD3 genomes

AF:

0.00000660

AC:

AN:

151468

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1447786

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

720048

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000660

AC:

AN:

151468

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73972

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000354

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

Cadd

Benign

Dann

Benign

0.89

DEOGEN2

Benign

0.12

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.025

M_CAP

Benign

0.012

MetaRNN

Benign

0.087

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.51

REVEL

Benign

0.25

Sift

Benign

0.21

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.20

MutPred

0.38

Loss of glycosylation at S41 (P = 0.0016);

MVP

0.77

MPC

0.65

ClinPred

0.020

GERP RS

-1.1

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Varity_R

0.044

gMVP

0.14

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over