chr2-218306468-T-C

Variant names:

• chr2-218306468-T-C
• rs2014615
• NM_015488.5:c.237-33315T>C

Variant summary

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

The NM_015488.5(PNKD):​c.237-33315T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,094 control chromosomes in the GnomAD database, including 30,064 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 0.63 (30064 hom., cov: 32)
• Consequence: PNKD NM_015488.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454
• Publications: 18 publications found

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]

PNKD Gene-Disease associations (from GenCC):

• paroxysmal nonkinesigenic dyskinesia 1

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
• Tourette syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000308453 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.681 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015488.5. 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
	PNKD	NM_015488.5	MANE Select	c.237-33315T>C		intron	N/A	NP_056303.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	ENST00000273077.9	TSL:1 MANE Select	c.237-33315T>C		intron	N/A	ENSP00000273077.4	Q8N490-1
	PNKD	ENST00000685415.1		c.354-33315T>C		intron	N/A	ENSP00000510415.1	A0A8I5KXK0
	PNKD	ENST00000901530.1		c.336-33315T>C		intron	N/A	ENSP00000571589.1

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95215 AN: 151976 Hom.: 30026 Cov.: 32

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.608

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.713

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.592

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

GnomAD4 genome AF: 0.627 AC: 95308 AN: 152094 Hom.: 30064 Cov.: 32 AF XY: 0.629 AC XY: 46779 AN XY: 74346

African (AFR) AF: 0.687 AC: 28516 AN: 41488

American (AMR) AF: 0.563 AC: 8601 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2166 AN: 3472

East Asian (EAS) AF: 0.609 AC: 3146 AN: 5164

South Asian (SAS) AF: 0.646 AC: 3118 AN: 4826

European-Finnish (FIN) AF: 0.713 AC: 7544 AN: 10576

Middle Eastern (MID) AF: 0.442 AC: 130 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40319 AN: 67974

Other (OTH) AF: 0.592 AC: 1249 AN: 2110

Alfa AF: 0.602 Hom.: 76466

Bravo AF: 0.618

Asia WGS AF: 0.672 AC: 2340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.29
PhyloP100		-0.45
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: rs2014615; hg19: chr2-219171191;