NM_145239.3(PRRT2):c.593_594del (p.Pro198fs) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jul 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:: RCV001009279.10

Allele description [Variation Report for NM_145239.3(PRRT2):c.593_594del (p.Pro198fs)]

NM_145239.3(PRRT2):c.593_594del (p.Pro198fs)

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.593_594del (p.Pro198fs)

HGVS:

NC_000016.10:g.29813647_29813648del
NG_032039.1:g.6560_6561del
NM_001256442.2:c.593_594del
NM_001256443.2:c.593_594del
NM_145239.3:c.593_594delMANE SELECT
NP_001243371.1:p.Pro198fs
NP_001243372.1:p.Pro198fs
NP_660282.2:p.Pro198fs
NC_000016.9:g.29824968_29824969del
NM_145239.2:c.593_594delCT

Protein change:

P198fs

Links:

dbSNP: rs1260966131

NCBI 1000 Genomes Browser:

rs1260966131

Molecular consequence:

NM_001256442.2:c.593_594del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001256443.2:c.593_594del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_145239.3:c.593_594del - 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
SCV001169101	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Likely pathogenic (Feb 26, 2019)	germline	clinical testing	Citation Link,
SCV004184552	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jul 1, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001169101

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Likely pathogenic
(Feb 26, 2019)

germline

clinical testing

Citation Link,

SCV004184552

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

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

Pathogenic
(Jul 1, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From GeneDx, SCV001169101.1

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

Description

The c.593_594delCT variant has been reported previously in an individual with infantile convulsions with paroxysmal choreoathetosis syndrome and speech delay who inherited c.593_594delCT from her asymptomatic mother and also had another PRRT2 pathogenic variant that was inherited from her father with PKD (Zeng et al., 2018). The deletion causes a frameshift starting with codon Proline 198, changes this amino acid to a Arginine residue and creates a premature Stop codon at position 26 of the new reading frame, denoted p.Pro198ArgfsX26. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Furthermore, the c.593_594delCT variant is not observed in large population cohorts (Lek et al., 2016). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

#	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, SCV004184552.9

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

Description

PRRT2: PVS1, PM2, PP4:Moderate, PS4:Moderate, BS2

#	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		2	not provided	not provided	not provided

Last Updated: Oct 20, 2024

ClinVar

Relating variation to medicine