rs12273350

chr11-125371150-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKNOX2	NM_001382323.2	c.227+3165G>A		intron_variant		ENST00000298282.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKNOX2	ENST00000298282.14	c.227+3165G>A		intron_variant		1	NM_001382323.2	P1

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

Gnomad4 AFR AF: 0.823

Gnomad4 AMR AF: 0.745

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.673

Gnomad4 FIN AF: 0.552

Gnomad4 NFE AF: 0.583

Gnomad4 OTH AF: 0.659

Alfa AF: 0.602 Hom.: 27691

Bravo AF: 0.691

Asia WGS AF: 0.741 AC: 2579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	19
Dann	Benign	0.80

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: rs12273350; hg19: chr11-125241046;