2-218270290-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000691799.1(PNKD):n.70+570G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 791,012 control chromosomes in the GnomAD database, including 1,828 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (1314 hom., cov: 33)
  • Exomes 𝑓: 0.0081 (514 hom.)
• Consequence: PNKD ENST00000691799.1 intron, non_coding_transcript
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.820

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 2-218270290-G-A is Benign according to our data. Variant chr2-218270290-G-A is described in ClinVar as [Benign]. Clinvar id is 1181914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNKD	ENST00000691799.1	n.70+570G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0725 AC: 11039 AN: 152230 Hom.: 1312 Cov.: 33

Gnomad AFR AF: 0.250

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0304

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00103

Gnomad OTH AF: 0.0602

GnomAD4 exome AF: 0.00808 AC: 5158 AN: 638664 Hom.: 514 Cov.: 8 AF XY: 0.00673 AC XY: 2215 AN XY: 328978

Gnomad4 AFR exome AF: 0.253

Gnomad4 AMR exome AF: 0.0177

Gnomad4 ASJ exome AF: 0.0000690

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000603

Gnomad4 FIN exome AF: 0.0000513

Gnomad4 NFE exome AF: 0.000714

Gnomad4 OTH exome AF: 0.0190

GnomAD4 genome AF: 0.0726 AC: 11066 AN: 152348 Hom.: 1314 Cov.: 33 AF XY: 0.0709 AC XY: 5284 AN XY: 74494

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.0303

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.000282

Gnomad4 NFE AF: 0.00103

Gnomad4 OTH AF: 0.0595

Alfa AF: 0.00744 Hom.: 176

Bravo AF: 0.0833

Asia WGS AF: 0.0150 AC: 52 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	9.3
Dann	Benign	0.91

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1877713; hg19: chr2-219135013;