Variant chr2-218340005-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.891

Variant links:

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 links:

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

CATIP-AS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein	UniProt
PNKD	NM_015488.5 linkuse as main transcript	c.353-24C>T		intron_variant		ENST00000273077.9	NP_056303.3
CATIP-AS2	NR_125777.1 linkuse as main transcript	n.120+11155G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9 linkuse as main transcript	c.353-24C>T		intron_variant		1	NM_015488.5	ENSP00000273077		Q8N490-1
CATIP-AS2	ENST00000411433.1 linkuse as main transcript	n.120+11155G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0548

AC:

8335

AN:

152104

Hom.:

320

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0602

AC XY:

42251

AN XY:

701294

show subpopulations

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.:

AF XY:

0.0574

AC XY:

4270

AN XY:

74412

show subpopulations

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.:

Bravo

AF:

0.0507

Asia WGS

AF:

0.126

AC:

438

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 21, 2018	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over