rs12288391

chr11-125254186-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382323.2(PKNOX2):c.-130+19071G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,024 control chromosomes in the GnomAD database, including 8,690 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 0.33 (8690 hom., cov: 32)
• Consequence: PKNOX2 NM_001382323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKNOX2	NM_001382323.2	c.-130+19071G>A		intron_variant		ENST00000298282.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKNOX2	ENST00000298282.14	c.-130+19071G>A		intron_variant		1	NM_001382323.2	P1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50469 AN: 151906 Hom.: 8678 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.332 AC: 50516 AN: 152024 Hom.: 8690 Cov.: 32 AF XY: 0.331 AC XY: 24603 AN XY: 74302

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.337

Gnomad4 OTH AF: 0.311

Alfa AF: 0.323 Hom.: 8016

Bravo AF: 0.322

Asia WGS AF: 0.267 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	7.1
Dann	Benign	0.68

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: rs12288391; hg19: chr11-125124082;