11-125305585-C-T

Variant names:

• chr11-125305585-C-T
• rs12273605
• NM_001382323.2:c.-129-26234C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382323.2(PKNOX2):​c.-129-26234C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,070 control chromosomes in the GnomAD database, including 3,517 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 0.20 (3517 hom., cov: 32)
• Consequence: PKNOX2 NM_001382323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.592

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

Verdict is Benign. Variant got -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 = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKNOX2	NM_001382323.2	c.-129-26234C>T		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.-129-26234C>T		intron_variant	Intron 2 of 12	1	NM_001382323.2	ENSP00000298282.8

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29804 AN: 151952 Hom.: 3498 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.0902

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.196 AC: 29852 AN: 152070 Hom.: 3517 Cov.: 32 AF XY: 0.199 AC XY: 14773 AN XY: 74340

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0902

Gnomad4 EAS AF: 0.328

Gnomad4 SAS AF: 0.185

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.174

Alfa AF: 0.134 Hom.: 751

Bravo AF: 0.194

Asia WGS AF: 0.302 AC: 1051 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.57

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

Publications

LitVar

Other links and lift over

dbSNP: rs12273605; hg19: chr11-125175481;