chr11-125254186-G-A

Variant names:

• chr11-125254186-G-A
• rs12288391
• NM_001382323.2:c.-130+19071G>A

Variant summary

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

The NM_001382323.2(PKNOX2):​c.-130+19071G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 152,024 control chromosomes in the GnomAD database, including 8,690 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 0.33 (8690 hom., cov: 32)
• Consequence: PKNOX2 NM_001382323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.372 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.-130+19071G>A		intron	N/A	NP_001369252.1
	PKNOX2	NM_001382324.1		c.-203+19071G>A		intron	N/A	NP_001369253.1
	PKNOX2	NM_001382325.1		c.-23+19071G>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.-130+19071G>A		intron	N/A	ENSP00000298282.8
	PKNOX2	ENST00000531212.5	TSL:4	c.-130+19071G>A		intron	N/A	ENSP00000434255.1
	PKNOX2	ENST00000527238.5	TSL:4	c.-203+14458G>A		intron	N/A	ENSP00000431599.1

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50469 AN: 151906 Hom.: 8678 Cov.: 32

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.234

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.314

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

GnomAD4 genome AF: 0.332 AC: 50516 AN: 152024 Hom.: 8690 Cov.: 32 AF XY: 0.331 AC XY: 24603 AN XY: 74302

African (AFR) AF: 0.376 AC: 15611 AN: 41464

American (AMR) AF: 0.216 AC: 3300 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1017 AN: 3468

East Asian (EAS) AF: 0.271 AC: 1397 AN: 5164

South Asian (SAS) AF: 0.236 AC: 1135 AN: 4814

European-Finnish (FIN) AF: 0.403 AC: 4250 AN: 10552

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.337 AC: 22917 AN: 67952

Other (OTH) AF: 0.311 AC: 656 AN: 2110

Alfa AF: 0.323 Hom.: 10494

Bravo AF: 0.322

Asia WGS AF: 0.267 AC: 931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	7.1
DANN	Benign	0.68
PhyloP100		0.58
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: rs12288391; hg19: chr11-125124082;