NM_145239.3:c.487C>T

Variant names:

• chr16-29813541-C-T
• rs387907127
• NM_145239.3:c.487C>T

Variant summary

Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PVS1 PM2 PP5_Moderate

The NM_145239.3(PRRT2):​c.487C>T​(p.Gln163*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PRRT2 NM_145239.3 stop_gained
• Clinical Significance: Pathogenic criteria provided, single submitter P:3
• Conservation: PhyloP100: 0.771
• Publications: 8 publications found

Genes affected

PRRT2 (HGNC:30500): (proline rich transmembrane protein 2) This gene encodes a transmembrane protein containing a proline-rich domain in its N-terminal half. Studies in mice suggest that it is predominantly expressed in brain and spinal cord in embryonic and postnatal stages. Mutations in this gene are associated with episodic kinesigenic dyskinesia-1. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ENSG00000280893 (HGNC:):

MVP-DT (HGNC:56029): (MVP divergent transcript)

ACMG classification

Our verdict: Pathogenic. The variant received 12 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 16-29813541-C-T is Pathogenic according to our data. Variant chr16-29813541-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 31176.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRRT2	NM_145239.3	c.487C>T	p.Gln163*	stop_gained	Exon 2 of 4	ENST00000358758.12	NP_660282.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRRT2	ENST00000358758.12	c.487C>T	p.Gln163*	stop_gained	Exon 2 of 4	1	NM_145239.3	ENSP00000351608.7
ENSG00000280893	ENST00000609618.2	n.487C>T		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000476774.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000150 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, single submitter

Submissions by phenotype

Episodic kinesigenic dyskinesia 1 Pathogenic:1

Dec 01, 2011

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Inborn genetic diseases Pathogenic:1

Jan 03, 2025

Ambry Genetics

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.487C>T (p.Q163*) alteration, located in exon 2 (coding exon 1) of the PRRT2 gene, consists of a C to T substitution at nucleotide position 487. This changes the amino acid from a glutamine (Q) to a stop codon at amino acid position 163. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant was identified in multiple individuals with features consistent with paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD/IC) and segregated with disease in at least one family (Wang, 2011). Based on the available evidence, this alteration is classified as pathogenic. -

Infantile convulsions and choreoathetosis Pathogenic:1

Dec 01, 2011

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.60	D
BayesDel_noAF	Pathogenic	0.52
CADD	Pathogenic	33
DANN	Uncertain	0.98
Eigen	Uncertain	0.26
Eigen_PC	Benign	-0.039
FATHMM_MKL	Benign	0.29	N
PhyloP100		0.77
Vest4		0.83
GERP RS		2.9
Mutation Taster		=0/200	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs387907127; hg19: chr16-29824862;