11-125306541-T-C

Variant names:

• chr11-125306541-T-C
• rs10893365
• NM_001382323.2:c.-129-25278T>C

Variant summary

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

The NM_001382323.2(PKNOX2):​c.-129-25278T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,190 control chromosomes in the GnomAD database, including 6,263 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 0.26 (6263 hom., cov: 33)
• Consequence: PKNOX2 NM_001382323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.16
• Publications: 9 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=-0.32).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.515 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.-129-25278T>C		intron	N/A	NP_001369252.1	Q96KN3-1
	PKNOX2	NM_001382324.1		c.-202-25278T>C		intron	N/A	NP_001369253.1	Q96KN3-1
	PKNOX2	NM_001382325.1		c.-22-44743T>C		intron	N/A	NP_001369254.1	Q96KN3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKNOX2	ENST00000298282.14	TSL:1 MANE Select	c.-129-25278T>C		intron	N/A	ENSP00000298282.8	Q96KN3-1
	PKNOX2	ENST00000878499.1		c.-129-25278T>C		intron	N/A	ENSP00000548558.1
	PKNOX2	ENST00000878493.1		c.-129-25278T>C		intron	N/A	ENSP00000548552.1

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39163 AN: 152070 Hom.: 6226 Cov.: 33

Gnomad AFR AF: 0.416

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.144

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.228

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

GnomAD4 genome AF: 0.258 AC: 39246 AN: 152190 Hom.: 6263 Cov.: 33 AF XY: 0.262 AC XY: 19460 AN XY: 74406

African (AFR) AF: 0.417 AC: 17301 AN: 41508

American (AMR) AF: 0.143 AC: 2193 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 505 AN: 3472

East Asian (EAS) AF: 0.531 AC: 2748 AN: 5174

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4818

European-Finnish (FIN) AF: 0.266 AC: 2817 AN: 10600

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11743 AN: 68006

Other (OTH) AF: 0.234 AC: 494 AN: 2112

Alfa AF: 0.226 Hom.: 785

Bravo AF: 0.257

Asia WGS AF: 0.434 AC: 1510 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	21
DANN	Benign	0.80
PhyloP100		1.2
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: rs10893365; hg19: chr11-125176437;