rs1017698

Positions:

• chr2-218305802-G-A
• chr2-218305802-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PNKD	NM_015488.5	c.237-33981G>A		intron_variant		ENST00000273077.9
PNKD	XM_017003771.2	c.237-33981G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNKD	ENST00000273077.9	c.237-33981G>A		intron_variant		1	NM_015488.5

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

Gnomad4 AFR AF: 0.370

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.608

Gnomad4 SAS AF: 0.645

Gnomad4 FIN AF: 0.714

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.522

Alfa AF: 0.576 Hom.: 44188

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

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: rs1017698; hg19: chr2-219170525;