ClinVar Genomic variation as it relates to human health
NM_144773.4(PROKR2):c.802C>T (p.Arg268Cys)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_144773.4(PROKR2):c.802C>T (p.Arg268Cys)
Variation ID: 282345 Accession: VCV000282345.16
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 20p12.3 20: 5302393 (GRCh38) [ NCBI UCSC ] 20: 5283039 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Dec 6, 2016 Feb 20, 2024 Jan 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_144773.4:c.802C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_658986.1:p.Arg268Cys missense NC_000020.11:g.5302393G>A NC_000020.10:g.5283039G>A NG_008132.2:g.16977C>T Q8NFJ6:p.Arg268Cys - Protein change
- R268C
- Other names
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- Canonical SPDI
- NC_000020.11:5302392:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.01258 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00391
Exome Aggregation Consortium (ExAC) 0.00468
1000 Genomes Project 0.01258
1000 Genomes Project 30x 0.01359
The Genome Aggregation Database (gnomAD) 0.01447
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01469
Trans-Omics for Precision Medicine (TOPMed) 0.01487
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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PROKR2 | - | - |
GRCh38 GRCh37 |
143 | 179 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV000330452.5 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Jun 12, 2017 | RCV000386257.6 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Jan 25, 2024 | RCV000712861.9 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(Jun 12, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000515863.2
First in ClinVar: Mar 08, 2017 Last updated: Apr 09, 2018 |
Comment:
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more)
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
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Benign
(Mar 02, 2018)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics Inc
Accession: SCV000843402.1
First in ClinVar: Oct 20, 2018 Last updated: Oct 20, 2018 |
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Benign
(Sep 15, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000333763.4
First in ClinVar: Dec 06, 2016 Last updated: Apr 09, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Hypogonadotropic hypogonadism 3 with or without anosmia
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000434471.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Benign
(Jan 25, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001000669.5
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Biased signaling through G-protein-coupled PROKR2 receptors harboring missense mutations. | Sbai O | FASEB journal : official publication of the Federation of American Societies for Experimental Biology | 2014 | PMID: 24830383 |
Germline prokineticin receptor 2 (PROKR2) variants associated with central hypogonadism cause differental modulation of distinct intracellular pathways. | Libri DV | The Journal of clinical endocrinology and metabolism | 2014 | PMID: 24276467 |
Greater prevalence of PROKR2 mutations in Kallmann syndrome patients from the Maghreb than in European patients. | Sarfati J | European journal of endocrinology | 2013 | PMID: 24031091 |
Variations in PROKR2, but not PROK2, are associated with hypopituitarism and septo-optic dysplasia. | McCabe MJ | The Journal of clinical endocrinology and metabolism | 2013 | PMID: 23386640 |
PROKR2 mutations in autosomal recessive Kallmann syndrome. | Tommiska J | Fertility and sterility | 2013 | PMID: 23200691 |
An informatics approach to analyzing the incidentalome. | Berg JS | Genetics in medicine : official journal of the American College of Medical Genetics | 2013 | PMID: 22995991 |
SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome. | Hanchate NK | PLoS genetics | 2012 | PMID: 22927827 |
Genetic overlap in Kallmann syndrome, combined pituitary hormone deficiency, and septo-optic dysplasia. | Raivio T | The Journal of clinical endocrinology and metabolism | 2012 | PMID: 22319038 |
Expression of PROKR1 and PROKR2 in human enteric neural precursor cells and identification of sequence variants suggest a role in HSCR. | Ruiz-Ferrer M | PloS one | 2011 | PMID: 21858136 |
A map of human genome variation from population-scale sequencing. | 1000 Genomes Project Consortium | Nature | 2010 | PMID: 20981092 |
Oligogenic basis of isolated gonadotropin-releasing hormone deficiency. | Sykiotis GP | Proceedings of the National Academy of Sciences of the United States of America | 2010 | PMID: 20696889 |
PROKR2 missense mutations associated with Kallmann syndrome impair receptor signalling activity. | Monnier C | Human molecular genetics | 2009 | PMID: 18826963 |
Loss-of-function mutations in the genes encoding prokineticin-2 or prokineticin receptor-2 cause autosomal recessive Kallmann syndrome. | Abreu AP | The Journal of clinical endocrinology and metabolism | 2008 | PMID: 18682503 |
Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. | Dodé C | PLoS genetics | 2006 | PMID: 17054399 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PROKR2 | - | - | - | - |
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Text-mined citations for rs78861628 ...
HelpRecord last updated Feb 28, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.