chr2-218340005-C-T

Variant names:

• chr2-218340005-C-T
• rs73088163
• NM_015488.5:c.353-24C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.891
• Publications: 3 publications found

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]

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

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PNKD	NM_015488.5	c.353-24C>T		intron_variant	Intron 3 of 9	ENST00000273077.9	NP_056303.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9	c.353-24C>T		intron_variant	Intron 3 of 9	1	NM_015488.5	ENSP00000273077.4

Frequencies

GnomAD3 genomes AF: 0.0548 AC: 8335 AN: 152104 Hom.: 320 Cov.: 31

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

GnomAD2 exomes AF: 0.0675 AC: 16898 AN: 250348 AF XY: 0.0704

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 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.: 25 AF XY: 0.0602 AC XY: 42251 AN XY: 701294

African (AFR) AF: 0.0410 AC: 1320 AN: 32222

American (AMR) AF: 0.0369 AC: 1649 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.0407 AC: 1048 AN: 25760

East Asian (EAS) AF: 0.123 AC: 4845 AN: 39374

South Asian (SAS) AF: 0.131 AC: 11095 AN: 84994

European-Finnish (FIN) AF: 0.0712 AC: 3801 AN: 53350

Middle Eastern (MID) AF: 0.0646 AC: 365 AN: 5652

European-Non Finnish (NFE) AF: 0.0501 AC: 53001 AN: 1057852

Other (OTH) AF: 0.0638 AC: 3728 AN: 58462

GnomAD4 genome AF: 0.0547 AC: 8332 AN: 152222 Hom.: 320 Cov.: 31 AF XY: 0.0574 AC XY: 4270 AN XY: 74412

African (AFR) AF: 0.0401 AC: 1665 AN: 41542

American (AMR) AF: 0.0388 AC: 594 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0449 AC: 156 AN: 3472

East Asian (EAS) AF: 0.167 AC: 861 AN: 5162

South Asian (SAS) AF: 0.141 AC: 677 AN: 4806

European-Finnish (FIN) AF: 0.0672 AC: 713 AN: 10618

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.0518 AC: 3522 AN: 68012

Other (OTH) AF: 0.0521 AC: 110 AN: 2112

Alfa AF: 0.0487 Hom.: 109

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

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 21, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.9
DANN	Benign	0.69
PhyloP100		0.89
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73088163; hg19: chr2-219204728; COSMIC: COSV51232295; COSMIC: COSV51232295;