2-218270227-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.40

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNKD	ENST00000691799.1	n.70+507C>T		intron_variant, non_coding_transcript_variant
AAMP	ENST00000444053.5			upstream_gene_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70677 AN: 152030 Hom.: 18481 Cov.: 35

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.: 16 AF XY: 0.565 AC XY: 332647 AN XY: 588870

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.: 35 AF XY: 0.471 AC XY: 35027 AN XY: 74374

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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	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

Other links and lift over

dbSNP: rs13419763; hg19: chr2-219134950; COSMIC: COSV50307800; COSMIC: COSV50307800;