NM_145239.3(PRRT2):c.649dup (p.Arg217fs) AND Inborn genetic diseases

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 20, 2018
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:: RCV002313738.8

Allele description

NM_145239.3(PRRT2):c.649dup (p.Arg217fs)

Genes:

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

Variant type:

Duplication

Cytogenetic location:

16p11.2

Genomic location:

Preferred name:

NM_145239.3(PRRT2):c.649dup (p.Arg217fs)

HGVS:

NC_000016.10:g.29813703dup
NG_032039.1:g.6616dup
NM_001256442.2:c.649dup
NM_001256443.2:c.649dup
NM_145239.3:c.649dupMANE SELECT
NP_001243371.1:p.Arg217fs
NP_001243372.1:p.Arg217fs
NP_660282.2:p.Arg217fs
NC_000016.9:g.29825015_29825016insC
NC_000016.9:g.29825024dup
NM_001256442.1:c.649dup
NM_001256442.1:c.649dupC
NM_001256442.2:c.649dup
NM_001256443.1:c.649dupC
NM_145239.2:c.649_650insC
NM_145239.2:c.649dupC
NM_145239.3:c.640_641insCMANE SELECT
NM_145239.3:c.649dupCMANE SELECT
p.Arg217Profs*8
p.Arg217ProfsX8
p.R217PfsX8
NP_660282.2:p.Arg217Profs*8

Nucleotide change:

649_650insC

Protein change:

R217fs

Links:

OMIM: 614386.0001

Molecular consequence:

NM_001256442.2:c.649dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001256443.2:c.649dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_145239.3:c.649dup - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000849074	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Pathogenic (Apr 20, 2018)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22101681, 22243967, 22399141, 22832103, 28074849 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000849074

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Pathogenic
(Apr 20, 2018)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

Exome sequencing identifies truncating mutations in PRRT2 that cause paroxysmal kinesigenic dyskinesia.

Chen WJ, Lin Y, Xiong ZQ, Wei W, Ni W, Tan GH, Guo SL, He J, Chen YF, Zhang QJ, Li HF, Lin Y, Murong SX, Xu J, Wang N, Wu ZY.

Nat Genet. 2011 Nov 20;43(12):1252-5. doi: 10.1038/ng.1008.

PubMed [citation]

PMID:: 22101681

PRRT2 mutations cause benign familial infantile epilepsy and infantile convulsions with choreoathetosis syndrome.

Heron SE, Grinton BE, Kivity S, Afawi Z, Zuberi SM, Hughes JN, Pridmore C, Hodgson BL, Iona X, Sadleir LG, Pelekanos J, Herlenius E, Goldberg-Stern H, Bassan H, Haan E, Korczyn AD, Gardner AE, Corbett MA, Gécz J, Thomas PQ, Mulley JC, Berkovic SF, et al.

Am J Hum Genet. 2012 Jan 13;90(1):152-60. doi: 10.1016/j.ajhg.2011.12.003.

PubMed [citation]

PMID:: 22243967
PMCID:: PMC3257886

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000849074.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (5)

Description

The c.649dupC pathogenic mutation, located in coding exon 1 of the PRRT2 gene, results from a duplication of C at nucleotide position 649, causing a translational frameshift with a predicted alternate stop codon (p.R217Pfs*8). This alteration has been detected in many families in the literature with paroxysmal kinesigenic dyskinesia with infantile convulsions (PKD or PKC), familial infantile convulsions and paroxysmal choreoathetosis (ICCA), and benign familial infantile seizures or epilepsy (BFIS or BFIE) (Chen WJ et al. Nat Genet. 2011; 43(12):1252-5; Heron SE et al. Am J Hum Genet. 2012; 90(1):152-60; Lee HY et al. Cell Rep. 2012; 1(1):2-12; Ono S et al. J Hum Genet. 2012; 57(5):338-41; Wang Y et al. Sci Rep, 2017 Jan;7:40319). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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

Last Updated: Apr 20, 2024

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