rs201804321

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001382323.2(PKNOX2):​c.665C>A​(p.Ala222Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000743 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A222V) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

PKNOX2
NM_001382323.2 missense

Scores

2
10
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.61
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PKNOX2NM_001382323.2 linkc.665C>A p.Ala222Glu missense_variant Exon 8 of 13 ENST00000298282.14 NP_001369252.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PKNOX2ENST00000298282.14 linkc.665C>A p.Ala222Glu missense_variant Exon 8 of 13 1 NM_001382323.2 ENSP00000298282.8 Q96KN3-1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152072
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000802
AC:
2
AN:
249472
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135358
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.00000752
AC:
11
AN:
1461846
Hom.:
0
Cov.:
32
AF XY:
0.0000110
AC XY:
8
AN XY:
727232
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.0000749
Gnomad4 NFE exome
AF:
0.00000630
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152190
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74406
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000684
Hom.:
0
ExAC
AF:
0.00000826
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.54
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.17
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.066
T
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.47
T
MetaSVM
Uncertain
-0.073
T
MutationAssessor
Benign
1.5
L
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-1.6
N
REVEL
Uncertain
0.51
Sift
Benign
0.067
T
Sift4G
Benign
0.37
T
Polyphen
0.65
P
Vest4
0.66
MutPred
0.34
Gain of solvent accessibility (P = 0.0674);
MVP
0.93
MPC
0.42
ClinPred
0.87
D
GERP RS
5.6
Varity_R
0.35
gMVP
0.50

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs201804321; hg19: chr11-125280168; API