rs73088163

chr2-218340005-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015488.5(PNKD):c.353-24C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0574 in 1,554,528 control chromosomes in the GnomAD database, including 3,275 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.055 (320 hom., cov: 31)
  • Exomes 𝑓: 0.058 (2955 hom.)
• Consequence: PNKD NM_015488.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.891

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]

CATIP-AS2 (HGNC:41079): (CATIP antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-218340005-C-T is Benign according to our data. Variant chr2-218340005-C-T is described in ClinVar as [Benign]. Clinvar id is 260660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNKD	NM_015488.5	c.353-24C>T		intron_variant		ENST00000273077.9
CATIP-AS2	NR_125777.1	n.120+11155G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNKD	ENST00000273077.9	c.353-24C>T		intron_variant		1	NM_015488.5
CATIP-AS2	ENST00000411433.1	n.120+11155G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0548 AC: 8335 AN: 152104 Hom.: 320 Cov.: 31

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0390

Gnomad ASJ AF: 0.0449

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0672

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0518

Gnomad OTH AF: 0.0531

GnomAD3 exomes AF: 0.0675 AC: 16898 AN: 250348 Hom.: 781 AF XY: 0.0704 AC XY: 9547 AN XY: 135578

Gnomad AFR exome AF: 0.0361

Gnomad AMR exome AF: 0.0368

Gnomad ASJ exome AF: 0.0448

Gnomad EAS exome AF: 0.165

Gnomad SAS exome AF: 0.132

Gnomad FIN exome AF: 0.0667

Gnomad NFE exome AF: 0.0509

Gnomad OTH exome AF: 0.0574

GnomAD4 exome AF: 0.0577 AC: 80852 AN: 1402306 Hom.: 2955 Cov.: 25 AF XY: 0.0602 AC XY: 42251 AN XY: 701294

Gnomad4 AFR exome AF: 0.0410

Gnomad4 AMR exome AF: 0.0369

Gnomad4 ASJ exome AF: 0.0407

Gnomad4 EAS exome AF: 0.123

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0712

Gnomad4 NFE exome AF: 0.0501

Gnomad4 OTH exome AF: 0.0638

GnomAD4 genome AF: 0.0547 AC: 8332 AN: 152222 Hom.: 320 Cov.: 31 AF XY: 0.0574 AC XY: 4270 AN XY: 74412

Gnomad4 AFR AF: 0.0401

Gnomad4 AMR AF: 0.0388

Gnomad4 ASJ AF: 0.0449

Gnomad4 EAS AF: 0.167

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.0672

Gnomad4 NFE AF: 0.0518

Gnomad4 OTH AF: 0.0521

Alfa AF: 0.0529 Hom.: 68

Bravo AF: 0.0507

Asia WGS AF: 0.126 AC: 438 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 21, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.9
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs73088163; hg19: chr2-219204728; COSMIC: COSV51232295; COSMIC: COSV51232295;