rs10893363

Variant names:

• chr11-125295883-A-G
• rs10893363
• NM_001382323.2:c.-129-35936A>G

Variant summary

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

The NM_001382323.2(PKNOX2):​c.-129-35936A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0917 in 152,104 control chromosomes in the GnomAD database, including 1,136 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 0.092 (1136 hom., cov: 32)
• Consequence: PKNOX2 NM_001382323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.556
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKNOX2	NM_001382323.2	c.-129-35936A>G		intron_variant	Intron 2 of 12	ENST00000298282.14	NP_001369252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKNOX2	ENST00000298282.14	c.-129-35936A>G		intron_variant	Intron 2 of 12	1	NM_001382323.2	ENSP00000298282.8

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13958 AN: 151986 Hom.: 1138 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.0648

Gnomad AMR AF: 0.0608

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.436

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0494

Gnomad OTH AF: 0.0934

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

GnomAD4 genome AF: 0.0917 AC: 13952 AN: 152104 Hom.: 1136 Cov.: 32 AF XY: 0.0960 AC XY: 7140 AN XY: 74352

African (AFR) AF: 0.126 AC: 5224 AN: 41472

American (AMR) AF: 0.0607 AC: 929 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 351 AN: 3466

East Asian (EAS) AF: 0.435 AC: 2240 AN: 5146

South Asian (SAS) AF: 0.203 AC: 978 AN: 4810

European-Finnish (FIN) AF: 0.0541 AC: 573 AN: 10596

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.0493 AC: 3355 AN: 68002

Other (OTH) AF: 0.0943 AC: 199 AN: 2110

Alfa AF: 0.0686 Hom.: 1236

Bravo AF: 0.0917

Asia WGS AF: 0.294 AC: 1019 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.097
DANN	Benign	0.68
PhyloP100		-0.56
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: rs10893363; hg19: chr11-125165779;