rs2014615

Positions:

• chr2-218306468-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000273077.9(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 ENST00000273077.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

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]

LOC105373881 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNKD	NM_015488.5	c.237-33315T>C		intron_variant		ENST00000273077.9	NP_056303.3
LOC105373881	XR_923914.3	n.306A>G		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9	c.237-33315T>C		intron_variant		1	NM_015488.5	ENSP00000273077

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

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.624

Gnomad4 EAS AF: 0.609

Gnomad4 SAS AF: 0.646

Gnomad4 FIN AF: 0.713

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.592

Alfa AF: 0.595 Hom.: 46430

Bravo AF: 0.618

Asia WGS AF: 0.672 AC: 2340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.29

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: rs2014615; hg19: chr2-219171191;