NM_001382323.2:c.936+1501A>G

Variant names:

• chr11-125413366-A-G
• rs7104304
• NM_001382323.2:c.936+1501A>G

Variant summary

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

The NM_001382323.2(PKNOX2):​c.936+1501A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,038 control chromosomes in the GnomAD database, including 16,026 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 0.45 (16026 hom., cov: 32)
• Consequence: PKNOX2 NM_001382323.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.211
• Publications: 1 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=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKNOX2	NM_001382323.2	c.936+1501A>G		intron_variant	Intron 10 of 12	ENST00000298282.14	NP_001369252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKNOX2	ENST00000298282.14	c.936+1501A>G		intron_variant	Intron 10 of 12	1	NM_001382323.2	ENSP00000298282.8

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68090 AN: 151920 Hom.: 16014 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.411

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.350

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.344

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.541

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.448 AC: 68136 AN: 152038 Hom.: 16026 Cov.: 32 AF XY: 0.437 AC XY: 32471 AN XY: 74318

African (AFR) AF: 0.331 AC: 13722 AN: 41464

American (AMR) AF: 0.411 AC: 6286 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1730 AN: 3462

East Asian (EAS) AF: 0.350 AC: 1795 AN: 5132

South Asian (SAS) AF: 0.539 AC: 2597 AN: 4816

European-Finnish (FIN) AF: 0.344 AC: 3638 AN: 10588

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.541 AC: 36763 AN: 67964

Other (OTH) AF: 0.483 AC: 1020 AN: 2112

Alfa AF: 0.503 Hom.: 24568

Bravo AF: 0.447

Asia WGS AF: 0.398 AC: 1387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	7.8
DANN	Benign	0.89
PhyloP100		-0.21
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: rs7104304; hg19: chr11-125283262;