NM_145239.3(PRRT2):c.649dup (p.Arg217fs) AND not provided

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

Germline classification:: Pathogenic (12 submissions)
Last evaluated:: Feb 1, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000188779.51

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)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000203360	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions)	Pathogenic (Apr 29, 2014)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22101681, 23180180, 23182655 Citation Link,
SCV000242403	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 23, 2020)	germline	clinical testing	Citation Link,
SCV000281646	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000614795	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Mar 6, 2023)	unknown	clinical testing	PubMed (21) [See all records that cite these PMIDs] 22870186, 23077017, 23077026, 22131361, 23077024, 22875091, 22209761, 24370076, 23771590, 25522171, 25502464, 22101681, 22243967, 22782515, 23126439, 23182655, 22120146, 22623405, 22399141, 11179027, 26467025
SCV001248447	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Feb 1, 2024)	germline	clinical testing	Citation Link,
SCV001715149	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 10, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 22101681, 22845787, 22243967, 25457817, 25741868
SCV001807268	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001905656	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001931576	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV002019531	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 7, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002036777	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV002818270	Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 17, 2022)	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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	87	not provided	not provided	1	not provided	clinical testing
not provided	germline	unknown	6	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Migraine with aura as the predominant phenotype in a family with a PRRT2 mutation.

Sheerin UM, Stamelou M, Charlesworth G, Shiner T, Spacey S, Valente EM, Wood NW, Bhatia KP.

J Neurol. 2013 Feb;260(2):656-60. doi: 10.1007/s00415-012-6747-4. Epub 2012 Nov 24. No abstract available.

PubMed [citation]

PMID:: 23180180
PMCID:: PMC4193291

PRRT2 mutations in paroxysmal kinesigenic dyskinesia with infantile convulsions in a Taiwanese cohort.

Lee YC, Lee MJ, Yu HY, Chen C, Hsu CH, Lin KP, Liao KK, Chang MH, Liao YC, Soong BW.

PLoS One. 2012;7(8):e38543. doi: 10.1371/journal.pone.0038543. Epub 2012 Aug 1.

PubMed [citation]

PMID:: 22870186
PMCID:: PMC3409860

See all PubMed Citations (25)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000203360.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	6	not provided	not provided	clinical testing	PubMed (3)

#	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		6	not provided	not provided	not provided

From GeneDx, SCV000242403.12

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

Description

Published functional studies indicate this variant results in decreased expression and altered cellular localization of the protein (Wu et al., 2014); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Recurrent pathogenic variant that accounts for approximately 77-93% of all pathogenic alleles in the PRRT2 gene; This variant is associated with the following publications: (PMID: 25522171, 23180180, 25502464, 23535490, 22877996, 22782515, 24661410, 22744660, 24370076, 27959697, 30182498, 30034362, 29250726, 31785815, 31901402, 31302675, 29655203, 26876767, 22101681, 25595153, 22243967, 23768507, 24074546, 22845787, 23771590, 23182655, 23126439, 24609974, 23532549, 22870186, 22623405, 27920401, 25915028, 27123484, 27172900, 28553402, 28097321, 28566192, 28525812, 29215089, 29778030, 29852413, 28018471, 29285950, 29302074, 30501978, 29132464, 30392205, 30125676, 30847922, 30814447, 31780880, 31737037, 31154286, 31722684, 32002278, 31216405, 32246320, 33126500, 34489640, 34298454, 32651081, 33391346, 33327426, 32613771, 33043084, 33258288, 32964447, 25667652, 25457817, 32860008, 33726816, 32237035)

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

From Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, SCV000281646.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	0.001855	not provided	not provided

From Athena Diagnostics, SCV000614795.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (21)

Description

This variant is expected to result in the loss of a functional protein. The frequency of this variant in the general population appears higher than would generally be expected for pathogenic variants in this gene, however, the data have failed quality metrics and thus are not useful in evaluating the pathogenicity of this variant (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). This variant has not been reported in control populations composed of more than 4,000 samples and varying ethnicities, which is consistent with the pathogenicity of this variant (PMID: 22243967, 22870186, 22875091, 23077024, 23077026, 22399141, 22209761, 22101681, 22131361, 25522171). This variant associates with various PRRT2-related disorders in multiple families, and is also reported to have reduced penetrance and variable expression between and within families (PMID: 23077026, 22782515, 23126439, 22120146, 22623405, 23077017, 23182655, 23771590, 24370076, 25502464). This variant appears to occur de novo in multiple individuals with various PRRT2-related disorders (PMID: 23077026, 22399141).

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

From CeGaT Center for Human Genetics Tuebingen, SCV001248447.20

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	87	not provided	not provided	clinical testing	not provided

Description

PRRT2: PVS1, PP1:Strong, PS2, PS4:Moderate

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		87	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV001715149.2

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

Description

PVS1, PS3, PS4, PP1, PP5

#	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

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001807268.1

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

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

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001905656.1

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

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

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001931576.1

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

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

From Revvity Omics, Revvity, SCV002019531.3

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

#	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

From Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) - VKGL Data-share Consensus, SCV002036777.1

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

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

From Al Jalila Children's Genomics Center, Al Jalila Childrens Speciality Hospital, SCV002818270.1

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

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

Last Updated: May 26, 2024

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