11-125434113-A-G

Variant names:

• chr11-125434113-A-G
• rs1783925
• ENST00000878493.1:c.*2721A>G

Variant summary

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

The ENST00000878493.1(PKNOX2):​c.*2721A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 151,984 control chromosomes in the GnomAD database, including 6,090 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 0.27 (6090 hom., cov: 30)
• Consequence: PKNOX2 ENST00000878493.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.227
• Publications: 15 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000878493.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKNOX2	ENST00000878493.1		c.*2721A>G		3_prime_UTR	Exon 12 of 12	ENSP00000548552.1
	PKNOX2	ENST00000878495.1		c.*2721A>G		3_prime_UTR	Exon 14 of 14	ENSP00000548554.1
	PKNOX2	ENST00000878494.1		c.*2721A>G		3_prime_UTR	Exon 10 of 10	ENSP00000548553.1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40409 AN: 151866 Hom.: 6089 Cov.: 30

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.394

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.266 AC: 40406 AN: 151984 Hom.: 6090 Cov.: 30 AF XY: 0.273 AC XY: 20256 AN XY: 74258

African (AFR) AF: 0.125 AC: 5183 AN: 41492

American (AMR) AF: 0.394 AC: 6011 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1020 AN: 3468

East Asian (EAS) AF: 0.375 AC: 1932 AN: 5158

South Asian (SAS) AF: 0.250 AC: 1205 AN: 4822

European-Finnish (FIN) AF: 0.383 AC: 4032 AN: 10534

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20059 AN: 67936

Other (OTH) AF: 0.271 AC: 570 AN: 2102

Alfa AF: 0.292 Hom.: 26817

Bravo AF: 0.263

Asia WGS AF: 0.362 AC: 1257 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.78
PhyloP100		0.23

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1783925; hg19: chr11-125304009; COSMIC: COSV53545401;