6-32188433-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002586.5(PBX2):​c.367C>G​(p.Leu123Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

PBX2
NM_002586.5 missense

Scores

1
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.70
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PBX2NM_002586.5 linkuse as main transcriptc.367C>G p.Leu123Val missense_variant 3/9 ENST00000375050.6 NP_002577.2 P40425A0A024RCR3
PBX2XM_047418839.1 linkuse as main transcriptc.22C>G p.Leu8Val missense_variant 2/8 XP_047274795.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PBX2ENST00000375050.6 linkuse as main transcriptc.367C>G p.Leu123Val missense_variant 3/91 NM_002586.5 ENSP00000364190.3 P40425
PBX2ENST00000478678.5 linkuse as main transcriptn.394C>G non_coding_transcript_exon_variant 3/61
PBX2ENST00000480254.1 linkuse as main transcriptn.427C>G non_coding_transcript_exon_variant 2/22
PBX2ENST00000496171.1 linkuse as main transcriptn.384C>G non_coding_transcript_exon_variant 1/42

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
33
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 30, 2024The c.367C>G (p.L123V) alteration is located in exon 3 (coding exon 3) of the PBX2 gene. This alteration results from a C to G substitution at nucleotide position 367, causing the leucine (L) at amino acid position 123 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.38
BayesDel_addAF
Benign
-0.044
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
26
DANN
Uncertain
0.99
DEOGEN2
Benign
0.13
T
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.42
FATHMM_MKL
Uncertain
0.95
D
M_CAP
Benign
0.016
T
MetaRNN
Uncertain
0.65
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
M
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.12
Sift
Benign
0.19
T
Sift4G
Benign
0.34
T
Polyphen
0.94
P
Vest4
0.72
MutPred
0.40
Loss of helix (P = 0.079);
MVP
0.31
MPC
1.4
ClinPred
0.95
D
GERP RS
5.0
Varity_R
0.34
gMVP
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-32156210; API