chr11-125301478-G-A

Variant names:

• chr11-125301478-G-A
• rs11220015
• NM_001382323.2:c.-129-30341G>A

Variant summary

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

The NM_001382323.2(PKNOX2):​c.-129-30341G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 151,454 control chromosomes in the GnomAD database, including 4,279 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 (4279 hom., cov: 31)
• Consequence: PKNOX2 NM_001382323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• Publications: 4 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=-0.38).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.373 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.-129-30341G>A		intron	N/A	NP_001369252.1
	PKNOX2	NM_001382324.1		c.-202-30341G>A		intron	N/A	NP_001369253.1
	PKNOX2	NM_001382325.1		c.-22-49806G>A		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.-129-30341G>A		intron	N/A	ENSP00000298282.8
	PKNOX2	ENST00000531212.5	TSL:4	c.-129-30341G>A		intron	N/A	ENSP00000434255.1
	PKNOX2	ENST00000527238.5	TSL:4	c.-202-30341G>A		intron	N/A	ENSP00000431599.1

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34092 AN: 151336 Hom.: 4263 Cov.: 31

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.225 AC: 34136 AN: 151454 Hom.: 4279 Cov.: 31 AF XY: 0.230 AC XY: 17014 AN XY: 73932

African (AFR) AF: 0.312 AC: 12846 AN: 41228

American (AMR) AF: 0.148 AC: 2253 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 397 AN: 3460

East Asian (EAS) AF: 0.388 AC: 1980 AN: 5108

South Asian (SAS) AF: 0.222 AC: 1070 AN: 4812

European-Finnish (FIN) AF: 0.300 AC: 3110 AN: 10368

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.175 AC: 11871 AN: 67956

Other (OTH) AF: 0.210 AC: 440 AN: 2098

Alfa AF: 0.128 Hom.: 303

Bravo AF: 0.220

Asia WGS AF: 0.338 AC: 1177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	16
DANN	Benign	0.76
PhyloP100		1.1
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: rs11220015; hg19: chr11-125171374;