rs10893347

Variant names:

• chr11-125193211-C-T
• rs10893347
• NM_001382323.2:c.-201+28435C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4 BA1

The NM_001382323.2(PKNOX2):​c.-201+28435C>T variant causes a intron change. The variant allele was found at a frequency of 0.221 in 152,194 control chromosomes in the GnomAD database, including 4,600 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 0.22 (4600 hom., cov: 33)
• Consequence: PKNOX2 NM_001382323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70
• Publications: 1 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.17).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKNOX2	NM_001382323.2	c.-201+28435C>T		intron_variant	Intron 1 of 12	ENST00000298282.14	NP_001369252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKNOX2	ENST00000298282.14	c.-201+28435C>T		intron_variant	Intron 1 of 12	1	NM_001382323.2	ENSP00000298282.8

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33707 AN: 152076 Hom.: 4605 Cov.: 33

Gnomad AFR AF: 0.0614

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.256

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

GnomAD4 genome AF: 0.221 AC: 33694 AN: 152194 Hom.: 4600 Cov.: 33 AF XY: 0.220 AC XY: 16332 AN XY: 74398

African (AFR) AF: 0.0612 AC: 2543 AN: 41546

American (AMR) AF: 0.197 AC: 3016 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 784 AN: 3466

East Asian (EAS) AF: 0.302 AC: 1561 AN: 5168

South Asian (SAS) AF: 0.201 AC: 970 AN: 4824

European-Finnish (FIN) AF: 0.290 AC: 3066 AN: 10590

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21032 AN: 67990

Other (OTH) AF: 0.258 AC: 544 AN: 2112

Alfa AF: 0.277 Hom.: 8180

Bravo AF: 0.210

Asia WGS AF: 0.200 AC: 699 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Benign	0.78
PhyloP100		4.7
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: rs10893347; hg19: chr11-125063107;