NM_145239.3(PRRT2):c.323_324del (p.Thr108fs) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Dec 23, 2019
Review status:: criteria provided, conflicting classifications

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:: RCV000278799.26

Allele description [Variation Report for NM_145239.3(PRRT2):c.323_324del (p.Thr108fs)]

NM_145239.3(PRRT2):c.323_324del (p.Thr108fs)

Genes:

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

Variant type:

Deletion

Cytogenetic location:

16p11.2

Genomic location:

Preferred name:

NM_145239.3(PRRT2):c.323_324del (p.Thr108fs)

HGVS:

NC_000016.10:g.29813377_29813378del
NG_032039.1:g.6290_6291del
NM_001256442.2:c.323_324del
NM_001256443.2:c.323_324del
NM_145239.3:c.323_324delMANE SELECT
NP_001243371.1:p.Thr108fs
NP_001243372.1:p.Thr108fs
NP_660282.2:p.Thr108fs
NC_000016.9:g.29824697_29824698del
NC_000016.9:g.29824698_29824699del
NM_145239.2:c.323_324del
NM_145239.2:c.323_324delCA

Protein change:

T108fs

Links:

dbSNP: rs886041327

NCBI 1000 Genomes Browser:

rs886041327

Molecular consequence:

NM_001256442.2:c.323_324del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001256443.2:c.323_324del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_145239.3:c.323_324del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000329741	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Dec 29, 2015)	germline	clinical testing	Citation Link,
SCV001150886	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Jun 1, 2018)	germline	clinical testing	Citation Link,
SCV001475994	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Dec 23, 2019)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29215089, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000329741

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Dec 29, 2015)

germline

clinical testing

Citation Link,

SCV001150886

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Jun 1, 2018)

germline

clinical testing

Citation Link,

SCV001475994

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Dec 23, 2019)

unknown

clinical testing

PubMed (2)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic analysis of benign familial epilepsies in the first year of life in a Chinese cohort.

Zeng Q, Yang X, Zhang J, Liu A, Yang Z, Liu X, Wu Y, Wu X, Wei L, Zhang Y.

J Hum Genet. 2018 Jan;63(1):9-18. doi: 10.1038/s10038-017-0359-x. Epub 2017 Nov 13.

PubMed [citation]

PMID:: 29215089
PMCID:: PMC8075886

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From GeneDx, SCV000329741.6

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

Description

The c.323_324delCA pathogenic variant in the PRRT2 gene has been reported previously in association with paroxysmal kinesigenic dyskinesia and benign familial infantile epilepsy (Yang et al., 2014; Seong et al., 2014). The deletion causes a frameshift starting with codon Threonine 108, changes this amino acid to a Serine residue and creates a premature Stop codon at position 25 of the new reading frame, denoted p.Thr108SerfsX25. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay.

#	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 CeGaT Center for Human Genetics Tuebingen, SCV001150886.27

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

From Athena Diagnostics, SCV001475994.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and not found in general population data.

#	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

Last Updated: Oct 20, 2024

ClinVar

Relating variation to medicine