11-125407598-C-T

Variant names:

• chr11-125407598-C-T
• rs7112365
• NM_001382323.2:c.589-2598C>T

Variant summary

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

The NM_001382323.2(PKNOX2):​c.589-2598C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 151,940 control chromosomes in the GnomAD database, including 1,864 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 0.15 (1864 hom., cov: 31)
• Consequence: PKNOX2 NM_001382323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.528
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKNOX2	NM_001382323.2	c.589-2598C>T		intron_variant	Intron 7 of 12	ENST00000298282.14	NP_001369252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKNOX2	ENST00000298282.14	c.589-2598C>T		intron_variant	Intron 7 of 12	1	NM_001382323.2	ENSP00000298282.8

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22190 AN: 151822 Hom.: 1858 Cov.: 31

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.371

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.121

Gnomad EAS AF: 0.0203

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.0773

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.125

Gnomad OTH AF: 0.151

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

GnomAD4 genome AF: 0.146 AC: 22225 AN: 151940 Hom.: 1864 Cov.: 31 AF XY: 0.142 AC XY: 10531 AN XY: 74254

African (AFR) AF: 0.230 AC: 9506 AN: 41402

American (AMR) AF: 0.116 AC: 1764 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 419 AN: 3468

East Asian (EAS) AF: 0.0204 AC: 105 AN: 5154

South Asian (SAS) AF: 0.0918 AC: 441 AN: 4802

European-Finnish (FIN) AF: 0.0773 AC: 818 AN: 10578

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.125 AC: 8480 AN: 67970

Other (OTH) AF: 0.150 AC: 316 AN: 2110

Alfa AF: 0.132 Hom.: 4637

Bravo AF: 0.154

Asia WGS AF: 0.0760 AC: 264 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.1
DANN	Benign	0.32
PhyloP100		0.53
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: rs7112365; hg19: chr11-125277494;