Variant 2-218270205-A-G 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 ENST00000691799.1(PNKD):n.70+485A>G 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 0.406 in 1,476,054 control chromosomes in the GnomAD database, including 122,563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.43 ( 14391 hom., cov: 34)

Exomes 𝑓: 0.40 ( 108172 hom. )

Consequence

PNKD
ENST00000691799.1 intron, non_coding_transcript

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.525

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:

AAMP (HGNC:18): (angio associated migratory cell protein) The gene is a member of the immunoglobulin superfamily. The encoded protein is associated with angiogenesis, with potential roles in endothelial tube formation and the migration of endothelial cells. It may also regulate smooth muscle cell migration via the RhoA pathway. The encoded protein can bind to heparin and may mediate heparin-sensitive cell adhesion. [provided by RefSeq, Oct 2014]

AAMP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 2-218270205-A-G is Benign according to our data. Variant chr2-218270205-A-G is described in ClinVar as [Benign]. Clinvar id is 1226098.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000691799.1 linkuse as main transcript	n.70+485A>G		intron_variant, non_coding_transcript_variant
AAMP	ENST00000444053.5 linkuse as main transcript			upstream_gene_variant		1		ENSP00000403343	P4

Frequencies

GnomAD3 genomes

AF:

0.431

AC:

65507

AN:

152048

Hom.:

14386

Cov.:

show subpopulations

Gnomad AFR

AF:

0.511

Gnomad AMI

AF:

0.429

Gnomad AMR

AF:

0.464

Gnomad ASJ

AF:

0.393

Gnomad EAS

AF:

0.396

Gnomad SAS

AF:

0.356

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.519

Gnomad NFE

AF:

0.405

Gnomad OTH

AF:

0.453

GnomAD4 exome

AF:

0.403

AC:

533569

AN:

1323888

Hom.:

108172

Cov.:

AF XY:

0.401

AC XY:

262177

AN XY:

653034

show subpopulations

Gnomad4 AFR exome

AF:

0.516

Gnomad4 AMR exome

AF:

0.464

Gnomad4 ASJ exome

AF:

0.391

Gnomad4 EAS exome

AF:

0.389

Gnomad4 SAS exome

AF:

0.354

Gnomad4 FIN exome

AF:

0.305

Gnomad4 NFE exome

AF:

0.406

Gnomad4 OTH exome

AF:

0.412

GnomAD4 genome

AF:

0.431

AC:

65542

AN:

152166

Hom.:

14391

Cov.:

AF XY:

0.427

AC XY:

31806

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.511

Gnomad4 AMR

AF:

0.463

Gnomad4 ASJ

AF:

0.393

Gnomad4 EAS

AF:

0.395

Gnomad4 SAS

AF:

0.357

Gnomad4 FIN

AF:

0.290

Gnomad4 NFE

AF:

0.405

Gnomad4 OTH

AF:

0.451

Alfa

AF:

0.421

Hom.:

4242

Bravo

AF:

0.448

Asia WGS

AF:

0.339

AC:

1176

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

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	Jul 05, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.7

DANN

Benign

0.73

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