NM_001382323.2:c.-129-30284A>G

Variant names:

• chr11-125301535-A-G
• rs11602925
• NM_001382323.2:c.-129-30284A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001382323.2(PKNOX2):​c.-129-30284A>G variant causes a intron change. The variant allele was found at a frequency of 0.225 in 151,744 control chromosomes in the GnomAD database, including 4,289 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 (4289 hom., cov: 31)
• Consequence: PKNOX2 NM_001382323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.94
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKNOX2	NM_001382323.2	c.-129-30284A>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.-129-30284A>G		intron_variant	Intron 2 of 12	1	NM_001382323.2	ENSP00000298282.8

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34075 AN: 151626 Hom.: 4273 Cov.: 31

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.225 AC: 34119 AN: 151744 Hom.: 4289 Cov.: 31 AF XY: 0.229 AC XY: 17011 AN XY: 74126

African (AFR) AF: 0.311 AC: 12850 AN: 41316

American (AMR) AF: 0.147 AC: 2243 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 395 AN: 3462

East Asian (EAS) AF: 0.388 AC: 1988 AN: 5128

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4818

European-Finnish (FIN) AF: 0.300 AC: 3151 AN: 10518

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11825 AN: 67950

Other (OTH) AF: 0.203 AC: 428 AN: 2104

Alfa AF: 0.196 Hom.: 636

Bravo AF: 0.219

Asia WGS AF: 0.338 AC: 1178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Benign	0.74
PhyloP100		3.9
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: rs11602925; hg19: chr11-125171431;