rs12273350

Variant names:

• chr11-125371150-G-A
• rs12273350
• NM_001382323.2:c.227+3165G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001382323.2(PKNOX2):​c.227+3165G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 152,088 control chromosomes in the GnomAD database, including 35,244 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 0.67 (35244 hom., cov: 32)
• Consequence: PKNOX2 NM_001382323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 10 publications found

Genes affected

PKNOX2 (HGNC:16714): (PBX/knotted 1 homeobox 2) Homeodomain proteins are sequence-specific transcription factors that share a highly conserved DNA-binding domain and play fundamental roles in cell proliferation, differentiation, and death. PKNOX2 belongs to the TALE (3-amino acid loop extension) class of homeodomain proteins characterized by a 3-amino acid extension between alpha helices 1 and 2 within the homeodomain (Imoto et al., 2001 [PubMed 11549286]).[supplied by OMIM, Oct 2009]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382323.2. 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
	PKNOX2	NM_001382323.2	MANE Select	c.227+3165G>A		intron	N/A	NP_001369252.1
	PKNOX2	NM_001382324.1		c.227+3165G>A		intron	N/A	NP_001369253.1
	PKNOX2	NM_001382325.1		c.227+3165G>A		intron	N/A	NP_001369254.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKNOX2	ENST00000298282.14	TSL:1 MANE Select	c.227+3165G>A		intron	N/A	ENSP00000298282.8
	PKNOX2	ENST00000558705.1	TSL:4	c.227+3165G>A		intron	N/A	ENSP00000453374.1
	PKNOX2	ENST00000530517.5	TSL:2	n.408+3165G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101861 AN: 151968 Hom.: 35173 Cov.: 32

Gnomad AFR AF: 0.822

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.689

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.552

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.583

Gnomad OTH AF: 0.655

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.671 AC: 101996 AN: 152088 Hom.: 35244 Cov.: 32 AF XY: 0.672 AC XY: 49956 AN XY: 74336

African (AFR) AF: 0.823 AC: 34137 AN: 41500

American (AMR) AF: 0.745 AC: 11389 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.583 AC: 2022 AN: 3466

East Asian (EAS) AF: 0.688 AC: 3554 AN: 5164

South Asian (SAS) AF: 0.673 AC: 3244 AN: 4822

European-Finnish (FIN) AF: 0.552 AC: 5836 AN: 10572

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.583 AC: 39595 AN: 67960

Other (OTH) AF: 0.659 AC: 1392 AN: 2112

Alfa AF: 0.615 Hom.: 77899

Bravo AF: 0.691

Asia WGS AF: 0.741 AC: 2579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Benign	0.80
PhyloP100		2.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs12273350; hg19: chr11-125241046;