11-125302697-A-G

Variant names:

• chr11-125302697-A-G
• rs750338
• NM_001382323.2:c.-129-29122A>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.-129-29122A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 152,108 control chromosomes in the GnomAD database, including 7,986 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 0.30 (7986 hom., cov: 33)
• Consequence: PKNOX2 NM_001382323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.647
• Publications: 21 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.532 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKNOX2	NM_001382323.2	MANE Select	c.-129-29122A>G		intron	N/A	NP_001369252.1
	PKNOX2	NM_001382324.1		c.-202-29122A>G		intron	N/A	NP_001369253.1
	PKNOX2	NM_001382325.1		c.-22-48587A>G		intron	N/A	NP_001369254.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKNOX2	ENST00000298282.14	TSL:1 MANE Select	c.-129-29122A>G		intron	N/A	ENSP00000298282.8
	PKNOX2	ENST00000531212.5	TSL:4	c.-129-29122A>G		intron	N/A	ENSP00000434255.1
	PKNOX2	ENST00000527238.5	TSL:4	c.-202-29122A>G		intron	N/A	ENSP00000431599.1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45762 AN: 151990 Hom.: 7959 Cov.: 33

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.285

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

GnomAD4 genome AF: 0.301 AC: 45835 AN: 152108 Hom.: 7986 Cov.: 33 AF XY: 0.302 AC XY: 22426 AN XY: 74350

African (AFR) AF: 0.454 AC: 18857 AN: 41502

American (AMR) AF: 0.196 AC: 3002 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2835 AN: 5166

South Asian (SAS) AF: 0.251 AC: 1207 AN: 4816

European-Finnish (FIN) AF: 0.278 AC: 2945 AN: 10590

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15512 AN: 67962

Other (OTH) AF: 0.289 AC: 610 AN: 2108

Alfa AF: 0.248 Hom.: 18744

Bravo AF: 0.303

Asia WGS AF: 0.430 AC: 1497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.55
DANN	Benign	0.53
PhyloP100		-0.65
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: rs750338; hg19: chr11-125172593;