Variant 2-218270227-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 ENST00000691799.1(PNKD):n.70+507C>T 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 0.552 in 1,336,888 control chromosomes in the GnomAD database, including 207,664 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 18505 hom., cov: 35)

Exomes 𝑓: 0.56 ( 189159 hom. )

Consequence

PNKD
ENST00000691799.1 intron, non_coding_transcript

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.40

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 2-218270227-C-T is Benign according to our data. Variant chr2-218270227-C-T is described in ClinVar as [Benign]. Clinvar id is 1290564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.613 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+507C>T		intron_variant, non_coding_transcript_variant
AAMP	ENST00000444053.5 linkuse as main transcript			upstream_gene_variant		1		ENSP00000403343	P4

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70677

AN:

152030

Hom.:

18481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.210

Gnomad AMI

AF:

0.532

Gnomad AMR

AF:

0.480

Gnomad ASJ

AF:

0.509

Gnomad EAS

AF:

0.600

Gnomad SAS

AF:

0.632

Gnomad FIN

AF:

0.686

Gnomad MID

AF:

0.380

Gnomad NFE

AF:

0.558

Gnomad OTH

AF:

0.450

GnomAD4 exome

AF:

0.563

AC:

666756

AN:

1184740

Hom.:

189159

Cov.:

AF XY:

0.565

AC XY:

332647

AN XY:

588870

show subpopulations

Gnomad4 AFR exome

AF:

0.200

Gnomad4 AMR exome

AF:

0.495

Gnomad4 ASJ exome

AF:

0.524

Gnomad4 EAS exome

AF:

0.609

Gnomad4 SAS exome

AF:

0.637

Gnomad4 FIN exome

AF:

0.676

Gnomad4 NFE exome

AF:

0.565

Gnomad4 OTH exome

AF:

0.542

GnomAD4 genome

AF:

0.465

AC:

70724

AN:

152148

Hom.:

18505

Cov.:

AF XY:

0.471

AC XY:

35027

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.210

Gnomad4 AMR

AF:

0.481

Gnomad4 ASJ

AF:

0.509

Gnomad4 EAS

AF:

0.600

Gnomad4 SAS

AF:

0.632

Gnomad4 FIN

AF:

0.686

Gnomad4 NFE

AF:

0.558

Gnomad4 OTH

AF:

0.454

Alfa

AF:

0.506

Hom.:

2596

Bravo

AF:

0.438

Asia WGS

AF:

0.621

AC:

2161

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	clinical testing	GeneDx	Jul 05, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.0

DANN

Benign

0.84

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