rs752070997

Variant names:

• chr6-32188397-C-A
• rs752070997
• NM_002586.5:c.403G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32188397-C-A
• chr6-32188397-C-T

Variant summary

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

The NM_002586.5(PBX2):​c.403G>T​(p.Gly135Cys) variant causes a missense change involving the alteration of a non-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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.13

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

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 rank	MANE	Protein	UniProt
PBX2	NM_002586.5	c.403G>T	p.Gly135Cys	missense_variant	Exon 3 of 9	ENST00000375050.6	NP_002577.2
PBX2	XM_047418839.1	c.58G>T	p.Gly20Cys	missense_variant	Exon 2 of 8		XP_047274795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBX2	ENST00000375050.6	c.403G>T	p.Gly135Cys	missense_variant	Exon 3 of 9	1	NM_002586.5	ENSP00000364190.3
PBX2	ENST00000478678.5	n.430G>T		non_coding_transcript_exon_variant	Exon 3 of 6	1
PBX2	ENST00000480254.1	n.463G>T		non_coding_transcript_exon_variant	Exon 2 of 2	2
PBX2	ENST00000496171.1	n.420G>T		non_coding_transcript_exon_variant	Exon 1 of 4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.030	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.40	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.68	D
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-5.2	D
REVEL	Benign	0.18
Sift	Benign	0.088	T
Sift4G	Uncertain	0.017	D
Polyphen		0.22	B
Vest4		0.71
MutPred		0.67		Loss of relative solvent accessibility (P = 0.0186);
MVP		0.46
MPC		1.0
ClinPred		0.99	D
GERP RS		5.0
Varity_R		0.25
gMVP		0.70

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

Other links and lift over

dbSNP: rs752070997; hg19: chr6-32156174;