NM_001126128.2(PROK2):c.163del (p.Ser54_Ile55insTer) AND not provided

Germline classification:: Pathogenic (6 submissions)
Last evaluated:: Nov 7, 2023
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:: RCV000516187.19

Allele description [Variation Report for NM_001126128.2(PROK2):c.163del (p.Ser54_Ile55insTer)]

NM_001126128.2(PROK2):c.163del (p.Ser54_Ile55insTer)

Gene:

PROK2:prokineticin 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p13

Genomic location:

Preferred name:

NM_001126128.2(PROK2):c.163del (p.Ser54_Ile55insTer)

HGVS:

NC_000003.12:g.71781526del
NG_008275.1:g.8681del
NM_001126128.2:c.163delMANE SELECT
NM_021935.4:c.163del
NP_001119600.1:p.Ser54_Ile55insTer
NP_068754.1:p.Ser54_Ile55insTer
NC_000003.11:g.71830677del
NC_000003.12:g.71781526_71781526delT
NM_001126128.1:c.163del
NM_001126128.1:c.163delA

Links:

OMIM: 607002.0003; dbSNP: rs554675432

NCBI 1000 Genomes Browser:

rs554675432

Molecular consequence:

NM_001126128.2:c.163del - nonsense - [Sequence Ontology: SO:0001587]
NM_021935.4:c.163del - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000343525	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Aug 1, 2016)	germline	clinical testing	Citation Link,
SCV000614789	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Nov 28, 2016)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 17959774, 24423319, 18285834, 23643382, 18559922, 18682503, 26467025
SCV001809562	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001817835	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 6, 2023)	germline	clinical testing	Citation Link,
SCV001958035	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV002247164	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 7, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 17959774, 18285834, 18559922, 23643382, 28492532

Help

Summary from all submissions

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

Citations

PubMed

Absence of central circadian pacemaker abnormalities in humans with loss of function mutation in prokineticin 2.

Balasubramanian R, Cohen DA, Klerman EB, Pignatelli D, Hall JE, Dwyer AA, Czeisler CA, Pitteloud N, Crowley WF.

J Clin Endocrinol Metab. 2014 Mar;99(3):E561-6. doi: 10.1210/jc.2013-2096. Epub 2014 Jan 1.

PubMed [citation]

PMID:: 24423319
PMCID:: PMC3942237

Loss-of-function mutations in the genes encoding prokineticin-2 or prokineticin receptor-2 cause autosomal recessive Kallmann syndrome.

Abreu AP, Trarbach EB, de Castro M, Frade Costa EM, Versiani B, Matias Baptista MT, Garmes HM, Mendonca BB, Latronico AC.

J Clin Endocrinol Metab. 2008 Oct;93(10):4113-8. doi: 10.1210/jc.2008-0958. Epub 2008 Aug 5.

PubMed [citation]

PMID:: 18682503

See all PubMed Citations (8)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000343525.4

#	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	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

From Athena Diagnostics, SCV000614789.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

#	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, SCV001809562.1

#	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 GeneDx, SCV001817835.2

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

Description

Nonsense 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; This variant is associated with the following publications: (PMID: 18559922, 18682503, 18285834, 24423319, 17959774, 29419413, 29165578, 29022642, 31200363, 31589614, 23643382, 31980526, 36268624)

#	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 Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001958035.1

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002247164.3

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

Description

This sequence change creates a premature translational stop signal (p.Ile55*) in the PROK2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PROK2 are known to be pathogenic (PMID: 17959774). This variant is present in population databases (rs554675432, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with Kallmann syndrome (PMID: 17959774, 18285834, 18559922, 23643382). It has also been observed to segregate with disease in related individuals. This variant is also known as I55fsX1. ClinVar contains an entry for this variant (Variation ID: 3603). For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Oct 13, 2024

ClinVar

Relating variation to medicine