NM_002586.5:c.*1772T>A

Variant names:

• chr6-32184610-A-T
• rs1800624
• NM_002586.5:c.*1772T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002586.5(PBX2):​c.*1772T>A variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 264,064 control chromosomes in the GnomAD database, including 8,196 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3854 hom., cov: 33)
  • Exomes 𝑓: 0.25 (4342 hom.)
• Consequence: PBX2 NM_002586.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.213
• Publications: 217 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]

ENSG00000273333 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.299 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX2	NM_002586.5	MANE Select	c.*1772T>A		downstream_gene	N/A	NP_002577.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PBX2	ENST00000375050.6	TSL:1 MANE Select	c.*1772T>A		downstream_gene	N/A	ENSP00000364190.3
	ENSG00000273333	ENST00000559458.2	TSL:2	n.*123T>A		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.210 AC: 29930 AN: 142242 Hom.: 3845 Cov.: 33

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.301

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.239

GnomAD4 exome AF: 0.252 AC: 30630 AN: 121722 Hom.: 4342 AF XY: 0.255 AC XY: 15535 AN XY: 60952

African (AFR) AF: 0.0547 AC: 196 AN: 3586

American (AMR) AF: 0.273 AC: 1058 AN: 3882

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1877 AN: 5186

East Asian (EAS) AF: 0.215 AC: 2286 AN: 10654

South Asian (SAS) AF: 0.144 AC: 324 AN: 2252

European-Finnish (FIN) AF: 0.303 AC: 2212 AN: 7290

Middle Eastern (MID) AF: 0.377 AC: 245 AN: 650

European-Non Finnish (NFE) AF: 0.257 AC: 20460 AN: 79714

Other (OTH) AF: 0.232 AC: 1972 AN: 8508

GnomAD4 genome AF: 0.210 AC: 29959 AN: 142342 Hom.: 3854 Cov.: 33 AF XY: 0.215 AC XY: 14936 AN XY: 69610

African (AFR) AF: 0.0508 AC: 1711 AN: 33666

American (AMR) AF: 0.307 AC: 4473 AN: 14574

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1216 AN: 3382

East Asian (EAS) AF: 0.148 AC: 719 AN: 4874

South Asian (SAS) AF: 0.169 AC: 777 AN: 4608

European-Finnish (FIN) AF: 0.313 AC: 3307 AN: 10558

Middle Eastern (MID) AF: 0.352 AC: 102 AN: 290

European-Non Finnish (NFE) AF: 0.250 AC: 16899 AN: 67508

Other (OTH) AF: 0.244 AC: 483 AN: 1978

Alfa AF: 0.103 Hom.: 186

Bravo AF: 0.192

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.6
DANN	Benign	0.78
PhyloP100		0.21
PromoterAI		-0.048	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1800624; hg19: chr6-32152387;