11-125309957-A-G

Variant names:

• chr11-125309957-A-G
• rs12284594
• NM_001382323.2:c.-129-21862A>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.-129-21862A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 152,010 control chromosomes in the GnomAD database, including 4,773 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 0.23 (4773 hom., cov: 32)
• Consequence: PKNOX2 NM_001382323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 11 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 = 0.498 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382323.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKNOX2	NM_001382323.2	MANE Select	c.-129-21862A>G		intron	N/A	NP_001369252.1
	PKNOX2	NM_001382324.1		c.-202-21862A>G		intron	N/A	NP_001369253.1
	PKNOX2	NM_001382325.1		c.-22-41327A>G		intron	N/A	NP_001369254.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKNOX2	ENST00000298282.14	TSL:1 MANE Select	c.-129-21862A>G		intron	N/A	ENSP00000298282.8
	PKNOX2	ENST00000878499.1		c.-129-21862A>G		intron	N/A	ENSP00000548558.1
	PKNOX2	ENST00000878493.1		c.-129-21862A>G		intron	N/A	ENSP00000548552.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35138 AN: 151892 Hom.: 4749 Cov.: 32

Gnomad AFR AF: 0.329

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.212

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

GnomAD4 genome AF: 0.232 AC: 35204 AN: 152010 Hom.: 4773 Cov.: 32 AF XY: 0.236 AC XY: 17498 AN XY: 74290

African (AFR) AF: 0.330 AC: 13669 AN: 41428

American (AMR) AF: 0.132 AC: 2013 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3470

East Asian (EAS) AF: 0.515 AC: 2649 AN: 5148

South Asian (SAS) AF: 0.250 AC: 1203 AN: 4814

European-Finnish (FIN) AF: 0.267 AC: 2817 AN: 10550

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11699 AN: 67996

Other (OTH) AF: 0.217 AC: 460 AN: 2116

Alfa AF: 0.192 Hom.: 5794

Bravo AF: 0.225

Asia WGS AF: 0.416 AC: 1448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.3
DANN	Benign	0.66
PhyloP100		0.36
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: rs12284594; hg19: chr11-125179853;