chr2-218305802-G-A

Variant names:

• chr2-218305802-G-A
• rs1017698
• NM_015488.5:c.237-33981G>A

Variant summary

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

The NM_015488.5(PNKD):​c.237-33981G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 151,942 control chromosomes in the GnomAD database, including 22,619 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 0.53 (22619 hom., cov: 31)
• Consequence: PNKD NM_015488.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• Publications: 24 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: Genomics England PanelApp, Orphanet
• Tourette syndrome

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNKD	NM_015488.5	c.237-33981G>A		intron_variant	Intron 2 of 9	ENST00000273077.9	NP_056303.3
PNKD	XM_017003771.2	c.237-33981G>A		intron_variant	Intron 2 of 8		XP_016859260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9	c.237-33981G>A		intron_variant	Intron 2 of 9	1	NM_015488.5	ENSP00000273077.4

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81169 AN: 151824 Hom.: 22598 Cov.: 31

Gnomad AFR AF: 0.370

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.624

Gnomad EAS AF: 0.607

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.420

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.522

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

GnomAD4 genome AF: 0.535 AC: 81231 AN: 151942 Hom.: 22619 Cov.: 31 AF XY: 0.539 AC XY: 40060 AN XY: 74260

African (AFR) AF: 0.370 AC: 15319 AN: 41442

American (AMR) AF: 0.525 AC: 7999 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.624 AC: 2164 AN: 3470

East Asian (EAS) AF: 0.608 AC: 3137 AN: 5158

South Asian (SAS) AF: 0.645 AC: 3105 AN: 4814

European-Finnish (FIN) AF: 0.714 AC: 7540 AN: 10558

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.592 AC: 40219 AN: 67948

Other (OTH) AF: 0.522 AC: 1104 AN: 2114

Alfa AF: 0.564 Hom.: 69645

Bravo AF: 0.512

Asia WGS AF: 0.654 AC: 2278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.0
DANN	Benign	0.90
PhyloP100		-2.0
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: rs1017698; hg19: chr2-219170525;