chr11-125385655-A-C

Variant names:

• chr11-125385655-A-C
• NM_001382323.2:c.332A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001382323.2(PKNOX2):​c.332A>C​(p.Asn111Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PKNOX2 NM_001382323.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.332A>C	p.Asn111Thr	missense	Exon 6 of 13	NP_001369252.1	Q96KN3-1
	PKNOX2	NM_001382324.1		c.332A>C	p.Asn111Thr	missense	Exon 7 of 14	NP_001369253.1	Q96KN3-1
	PKNOX2	NM_001382325.1		c.332A>C	p.Asn111Thr	missense	Exon 5 of 12	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.332A>C	p.Asn111Thr	missense	Exon 6 of 13	ENSP00000298282.8	Q96KN3-1
	PKNOX2	ENST00000878499.1		c.332A>C	p.Asn111Thr	missense	Exon 6 of 14	ENSP00000548558.1
	PKNOX2	ENST00000878493.1		c.332A>C	p.Asn111Thr	missense	Exon 5 of 12	ENSP00000548552.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	23
DANN	Benign	0.70
DEOGEN2	Benign	0.025	T
Eigen	Benign	0.034
Eigen_PC	Uncertain	0.22
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0087	T
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.6
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.11
Sift	Benign	0.93	T
Sift4G	Benign	1.0	T
Polyphen		0.073	B
Vest4		0.81
MutPred		0.42		Loss of loop (P = 0.0804)
MVP		0.56
MPC		0.31
ClinPred		0.82	D
GERP RS		5.5
Varity_R		0.17
gMVP		0.42
Mutation Taster		=30/70	disease causing

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

hg19: chr11-125255551;