2-218331076-G-A

Position:

• chr2-218331076-G-A

Variant summary

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

The NM_015488.5(PNKD):​c.237-8707G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.462 in 152,104 control chromosomes in the GnomAD database, including 16,759 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (16759 hom., cov: 32)
• Consequence: PNKD NM_015488.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.334

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:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 2-218331076-G-A is Benign according to our data. Variant chr2-218331076-G-A is described in ClinVar as [Benign]. Clinvar id is 1600301.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNKD	NM_015488.5	c.237-8707G>A		intron_variant		ENST00000273077.9	NP_056303.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9	c.237-8707G>A		intron_variant		1	NM_015488.5	ENSP00000273077.4

Frequencies

GnomAD3 genomes AF: 0.462 AC: 70148 AN: 151986 Hom.: 16733 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.465

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.627

Gnomad FIN AF: 0.558

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.456

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.462 AC: 70205 AN: 152104 Hom.: 16759 Cov.: 32 AF XY: 0.467 AC XY: 34755 AN XY: 74352

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.465

Gnomad4 EAS AF: 0.591

Gnomad4 SAS AF: 0.627

Gnomad4 FIN AF: 0.558

Gnomad4 NFE AF: 0.491

Gnomad4 OTH AF: 0.459

Alfa AF: 0.490 Hom.: 37996

Bravo AF: 0.450

Asia WGS AF: 0.640 AC: 2228 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Paroxysmal nonkinesigenic dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.3
DANN	Benign	0.91

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: rs10932775; hg19: chr2-219195799;