NM_145239.3(PRRT2):c.431C>T (p.Pro144Leu) AND Episodic kinesigenic dyskinesia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 4, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002231213.12

Allele description [Variation Report for NM_145239.3(PRRT2):c.431C>T (p.Pro144Leu)]

NM_145239.3(PRRT2):c.431C>T (p.Pro144Leu)

Genes:

MVP-DT:MVP divergent transcript [Gene - HGNC]
PRRT2:proline rich transmembrane protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16p11.2

Genomic location:

Preferred name:

NM_145239.3(PRRT2):c.431C>T (p.Pro144Leu)

HGVS:

NC_000016.10:g.29813485C>T
NG_032039.1:g.6398C>T
NM_001256442.2:c.431C>T
NM_001256443.2:c.431C>T
NM_145239.3:c.431C>TMANE SELECT
NP_001243371.1:p.Pro144Leu
NP_001243372.1:p.Pro144Leu
NP_660282.2:p.Pro144Leu
NC_000016.9:g.29824806C>T
NM_145239.2:c.431C>T

Protein change:

P144L

Links:

dbSNP: rs1317648011

NCBI 1000 Genomes Browser:

rs1317648011

Molecular consequence:

NM_001256442.2:c.431C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001256443.2:c.431C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_145239.3:c.431C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Episodic kinesigenic dyskinesia (EKD)
Synonyms:: Familial paroxysmal dystonia; Paroxysmal kinesigenic dyskinesia
Identifiers:: MONDO: MONDO:0044202; MedGen: C1868682; Orphanet: 98809; OMIM: PS128200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000645427	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 4, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000645427

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 4, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000645427.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 144 of the PRRT2 protein (p.Pro144Leu). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PRRT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 451350). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PRRT2 protein function with a negative predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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