2-218341566-G-T

Position:

• chr2-218341566-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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.39

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)

ACMG classification

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
PNKD	NM_015488.5	c.557G>T	p.Arg186Leu	missense_variant	6/10	ENST00000273077.9	NP_056303.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9	c.557G>T	p.Arg186Leu	missense_variant	6/10	1	NM_015488.5	ENSP00000273077.4

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

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

Other links and lift over

dbSNP: rs143162613; hg19: chr2-219206289;