rs999

Variant names:

• chr6-32186109-C-A
• rs999
• NM_002586.5:c.*273G>T

Your query was ambiguous. Multiple possible variants found:

• chr6-32186109-C-A
• chr6-32186109-C-G
• chr6-32186109-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002586.5(PBX2):​c.*273G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000833 in 479,944 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000061 (0 hom.)
• Consequence: PBX2 NM_002586.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• 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]

ENSG00000273333 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PBX2	NM_002586.5	c.*273G>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000375050.6	NP_002577.2
PBX2	XM_047418839.1	c.*273G>T		3_prime_UTR_variant	Exon 8 of 8		XP_047274795.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PBX2	ENST00000375050.6	c.*273G>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_002586.5	ENSP00000364190.3
ENSG00000273333	ENST00000559458.2	n.-227G>T		upstream_gene_variant		2
PBX2	ENST00000495300.1	n.*147G>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151516 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000486

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000609 AC: 2 AN: 328428 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 170254

African (AFR) AF: 0.000105 AC: 1 AN: 9562

American (AMR) AF: 0.00 AC: 0 AN: 11632

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11050

East Asian (EAS) AF: 0.00 AC: 0 AN: 25246

South Asian (SAS) AF: 0.00 AC: 0 AN: 23408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1532

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 202234

Other (OTH) AF: 0.0000497 AC: 1 AN: 20104

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151516 Hom.: 0 Cov.: 31 AF XY: 0.0000271 AC XY: 2 AN XY: 73924

African (AFR) AF: 0.0000486 AC: 2 AN: 41158

American (AMR) AF: 0.00 AC: 0 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67946

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.5
DANN	Benign	0.59
PhyloP100		0.25
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.95

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

dbSNP: rs999; hg19: chr6-32153886;