NM_198859.4(PRICKLE2):c.1813G>T (p.Val605Phe) AND Progressive myoclonic epilepsy type 5

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 11, 2011
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000023710.5

Allele description [Variation Report for NM_198859.4(PRICKLE2):c.1813G>T (p.Val605Phe)]

NM_198859.4(PRICKLE2):c.1813G>T (p.Val605Phe)

Genes:

PRICKLE2-AS1:PRICKLE2 antisense RNA 1 [Gene - HGNC]
PRICKLE2:prickle planar cell polarity protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p14.1

Genomic location:

Preferred name:

NM_198859.4(PRICKLE2):c.1813G>T (p.Val605Phe)

HGVS:

NC_000003.12:g.64099773C>A
NG_031930.1:g.130683G>T
NM_001370528.1:c.1813G>T
NM_198859.4:c.1813G>TMANE SELECT
NP_001357457.1:p.Val605Phe
NP_942559.1:p.Val605Phe
NC_000003.11:g.64085449C>A
NM_198859.3:c.1813G>T
NR_045697.1:n.3147C>A
Q7Z3G6:p.Val605Phe

Protein change:

V605F; VAL605PHE

Links:

UniProtKB: Q7Z3G6#VAR_065584; OMIM: 608501.0002; dbSNP: rs387906989

NCBI 1000 Genomes Browser:

rs387906989

Molecular consequence:

NM_001370528.1:c.1813G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_198859.4:c.1813G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_045697.1:n.3147C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Progressive myoclonic epilepsy type 5
Identifiers:: MedGen: C5190799; Orphanet: 402082

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000045001	OMIM	no assertion criteria provided	Uncertain significance (Feb 11, 2011)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 26942291, 21276947, 26942292

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000045001

OMIM

no assertion criteria provided

Uncertain significance
(Feb 11, 2011)

germline

literature only

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

PRICKLE2 Mutations Might Not Be Involved in Epilepsy.

Sandford E, Bird TD, Li JZ, Burmeister M.

Am J Hum Genet. 2016 Mar 3;98(3):588-589. doi: 10.1016/j.ajhg.2016.01.009. No abstract available.

PubMed [citation]

PMID:: 26942291
PMCID:: PMC4800039

Mutations in prickle orthologs cause seizures in flies, mice, and humans.

Tao H, Manak JR, Sowers L, Mei X, Kiyonari H, Abe T, Dahdaleh NS, Yang T, Wu S, Chen S, Fox MH, Gurnett C, Montine T, Bird T, Shaffer LG, Rosenfeld JA, McConnell J, Madan-Khetarpal S, Berry-Kravis E, Griesbach H, Saneto RP, Scott MP, et al.

Am J Hum Genet. 2011 Feb 11;88(2):138-49. doi: 10.1016/j.ajhg.2010.12.012. Epub 2011 Feb 3.

PubMed [citation]

PMID:: 21276947
PMCID:: PMC3035715

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000045001.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

Description

This variant, formerly titled EPILEPSY, PROGRESSIVE MYOCLONIC, 5 based on the findings of Tao et al. (2011), has been reclassified based on the findings of Sandford et al. (2016).

In a male patient with myoclonic seizures, Tao et al. (2011) identified a heterozygous 1813G-T transversion in the PRICKLE2 gene, resulting in a val605-to-phe (V605F) substitution. Studies of the orthologous V605F variant in zebrafish embryos showed that it resulted in decreased prickle2 activity compared to wildtype, as measured by convergent-extension movements during gastrulation. In addition, the V605F-variant protein was less active in stimulating calcium release compared to wildtype.

Sandford et al. (2016) stated that the PRICKLE2 V605F variant identified in a patient by Tao et al. (2011) appears twice in the ExAC database, and thus is not consistent with its being pathogenic. In a response, Mahajan and Bassuk (2016) maintained that the PRICKLE2 variant identified by Tao et al. (2011) contributed to the phenotype in the patient.

#	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	not provided	not provided	not provided

Last Updated: May 26, 2024

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