NM_002586.5:c.173A>G

Variant names:

• chr6-32189743-T-C
• NM_002586.5:c.173A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002586.5(PBX2):​c.173A>G​(p.Gln58Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PBX2 NM_002586.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.07
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.173A>G	p.Gln58Arg	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.173A>G	p.Gln58Arg	missense	Exon 1 of 9	ENSP00000364190.3	P40425
	PBX2	ENST00000478678.5	TSL:1	n.200A>G		non_coding_transcript_exon	Exon 1 of 6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.47
BayesDel_addAF	Benign	-0.066	T
BayesDel_noAF	Benign	-0.33
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.29	T
Eigen	Uncertain	0.58
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		4.1
PrimateAI	Pathogenic	0.87	D
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.23
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.011	D
Polyphen		0.99	D
Vest4		0.35
MutPred		0.60		Gain of MoRF binding (P = 0.0265)
MVP		0.52
MPC		1.2
ClinPred		0.96	D
GERP RS		3.9
PromoterAI		0.046	Neutral
Varity_R		0.10
gMVP		0.44
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

hg19: chr6-32157520;