rs600702

Variant names:

• chr11-125194718-G-T
• rs600702
• NM_001382323.2:c.-201+29942G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382323.2(PKNOX2):​c.-201+29942G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,062 control chromosomes in the GnomAD database, including 3,803 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 0.21 (3803 hom., cov: 32)
• Consequence: PKNOX2 NM_001382323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.131
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.315 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.-201+29942G>T		intron	N/A	NP_001369252.1	Q96KN3-1
	PKNOX2	NM_001382324.1		c.-274+29942G>T		intron	N/A	NP_001369253.1	Q96KN3-1
	PKNOX2	NM_001382325.1		c.-94+29942G>T		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.-201+29942G>T		intron	N/A	ENSP00000298282.8	Q96KN3-1
	PKNOX2	ENST00000878499.1		c.-201+29942G>T		intron	N/A	ENSP00000548558.1
	PKNOX2	ENST00000878493.1		c.-130+29942G>T		intron	N/A	ENSP00000548552.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31226 AN: 151944 Hom.: 3806 Cov.: 32

Gnomad AFR AF: 0.0949

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.205 AC: 31219 AN: 152062 Hom.: 3803 Cov.: 32 AF XY: 0.204 AC XY: 15178 AN XY: 74324

African (AFR) AF: 0.0946 AC: 3926 AN: 41488

American (AMR) AF: 0.317 AC: 4843 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1103 AN: 3470

East Asian (EAS) AF: 0.197 AC: 1016 AN: 5162

South Asian (SAS) AF: 0.329 AC: 1585 AN: 4824

European-Finnish (FIN) AF: 0.135 AC: 1422 AN: 10572

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.243 AC: 16519 AN: 67962

Other (OTH) AF: 0.229 AC: 482 AN: 2108

Alfa AF: 0.222 Hom.: 731

Bravo AF: 0.213

Asia WGS AF: 0.234 AC: 812 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.6
DANN	Benign	0.79
PhyloP100		0.13
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: rs600702; hg19: chr11-125064614;