Variant 2-218340003-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_015488.5(PNKD):c.353-26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00385 in 1,547,212 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0040 ( 29 hom. )

Consequence

PNKD
NM_015488.5 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.60

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:):

CATIP-AS2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-218340003-C-T is Benign according to our data. Variant chr2-218340003-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 260661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNKD	NM_015488.5 linkuse as main transcript	c.353-26C>T		intron_variant		ENST00000273077.9	NP_056303.3	Q8N490-1A0A024R415

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9 linkuse as main transcript	c.353-26C>T		intron_variant		1	NM_015488.5	ENSP00000273077.4		Q8N490-1

Frequencies

GnomAD3 genomes

AF:

0.00293

AC:

445

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00584

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00388

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00328

AC:

822

AN:

250272

Hom.:

AF XY:

0.00313

AC XY:

424

AN XY:

135554

show subpopulations

Gnomad AFR exome

AF:

0.000557

Gnomad AMR exome

AF:

0.00241

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000916

Gnomad FIN exome

AF:

0.00764

Gnomad NFE exome

AF:

0.00459

Gnomad OTH exome

AF:

0.00311

GnomAD4 exome

AF:

0.00396

AC:

5519

AN:

1394960

Hom.:

Cov.:

AF XY:

0.00389

AC XY:

2716

AN XY:

697652

show subpopulations

Gnomad4 AFR exome

AF:

0.000623

Gnomad4 AMR exome

AF:

0.00226

Gnomad4 ASJ exome

AF:

0.0000389

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00115

Gnomad4 FIN exome

AF:

0.00797

Gnomad4 NFE exome

AF:

0.00445

Gnomad4 OTH exome

AF:

0.00338

GnomAD4 genome

AF:

0.00292

AC:

445

AN:

152252

Hom.:

Cov.:

AF XY:

0.00334

AC XY:

249

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00517

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00584

Gnomad4 NFE

AF:

0.00388

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00287

Hom.:

Bravo

AF:

0.00277

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.28

DANN

Benign

0.65

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

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