2-218341566-G-T

Variant summary

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

The NM_015488.5(PNKD):​c.557G>T​(p.Arg186Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000138 in 1,450,218 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PNKD
NM_015488.5 missense

Scores

1
11
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.39
Variant links:
Genes affected
PNKD (HGNC:9153): (PNKD metallo-beta-lactamase domain containing) This gene is thought to play a role in the regulation of myofibrillogenesis. Mutations in this gene have been associated with the movement disorder paroxysmal non-kinesigenic dyskinesia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
CATIP-AS2 (HGNC:41079): (CATIP antisense RNA 2)

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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/exons MANE Protein UniProt
PNKDNM_015488.5 linkc.557G>T p.Arg186Leu missense_variant 6/10 ENST00000273077.9 NP_056303.3 Q8N490-1A0A024R415

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PNKDENST00000273077.9 linkc.557G>T p.Arg186Leu missense_variant 6/101 NM_015488.5 ENSP00000273077.4 Q8N490-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000138
AC:
2
AN:
1450218
Hom.:
0
Cov.:
31
AF XY:
0.00000139
AC XY:
1
AN XY:
720154
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:
0.00
Gnomad4 NFE exome
AF:
0.00000181
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.030
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.63
D;.;.
Eigen
Benign
0.085
Eigen_PC
Benign
0.18
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Uncertain
0.25
D
MetaRNN
Uncertain
0.48
T;T;T
MetaSVM
Uncertain
0.66
D
MutationAssessor
Benign
1.4
L;.;.
PrimateAI
Uncertain
0.54
T
PROVEAN
Uncertain
-3.7
D;D;D
REVEL
Uncertain
0.60
Sift
Benign
0.084
T;T;D
Sift4G
Benign
0.20
T;T;D
Polyphen
0.13
B;B;.
Vest4
0.50
MutPred
0.47
Loss of MoRF binding (P = 0.0183);.;.;
MVP
0.80
MPC
0.23
ClinPred
0.98
D
GERP RS
4.1
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.0
Varity_R
0.43
gMVP
0.68

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: rs143162613; hg19: chr2-219206289; API