ClinVar Genomic variation as it relates to human health
NM_144773.4(PROKR2):c.151G>A (p.Ala51Thr)
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.
Uncertain significance(1); Benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_144773.4(PROKR2):c.151G>A (p.Ala51Thr)
Variation ID: 338865 Accession: VCV000338865.22
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 20p12.3 20: 5314219 (GRCh38) [ NCBI UCSC ] 20: 5294865 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Apr 15, 2024 Jan 29, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_144773.4:c.151G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_658986.1:p.Ala51Thr missense NC_000020.11:g.5314219C>T NC_000020.10:g.5294865C>T NG_008132.2:g.5151G>A - Protein change
- A51T
- Other names
- -
- Canonical SPDI
- NC_000020.11:5314218:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
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.
-
0.00679 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00077
Trans-Omics for Precision Medicine (TOPMed) 0.00110
The Genome Aggregation Database (gnomAD) 0.00303
Exome Aggregation Consortium (ExAC) 0.00419
The Genome Aggregation Database (gnomAD), exomes 0.00449
1000 Genomes Project 30x 0.00562
1000 Genomes Project 0.00679
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 | ||
---|---|---|---|---|---|---|
HI score
Help
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. |
|||
PROKR2 | - | - |
GRCh38 GRCh37 |
147 | 183 |
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. |
---|---|---|---|---|
Benign (1) |
criteria provided, single submitter
|
Mar 6, 2018 | RCV000405604.5 | |
Uncertain significance (1) |
criteria provided, single submitter
|
Jan 30, 2015 | RCV000622788.2 | |
Benign (4) |
criteria provided, multiple submitters, no conflicts
|
Jan 29, 2024 | RCV000861011.14 | |
Benign (1) |
no assertion criteria provided
|
- | RCV001699378.2 |
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. |
|
---|---|---|---|---|---|
Benign
(Mar 06, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Hypogonadotropic hypogonadism 3 with or without anosmia
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000434481.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
Uncertain significance
(Jan 30, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary disease
Affected status: yes
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000740791.2
First in ClinVar: Apr 15, 2018 Last updated: Dec 11, 2022 |
Comment:
Lines of evidence used in support of classification: CANDIDATE: Alteration(s) of Potential Clinical Relevance Detected
Clinical Features:
Gastrointestinal (child onset) (present) , Genitourinary (child onset) (present)
Family history: yes
Sex: male
Ethnicity/Population group: European-origin
Segregation observed: yes
|
|
Benign
(Jan 29, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001001209.5
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
|
|
Benign
(Nov 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004149843.4
First in ClinVar: Nov 20, 2023 Last updated: Apr 15, 2024 |
Comment:
PROKR2: BP4, BS1, BS2
Number of individuals with the variant: 1
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001798827.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001917477.1 First in ClinVar: Sep 25, 2021 Last updated: Sep 25, 2021 |
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001954105.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
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 |
---|---|---|---|---|
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 |
PROK2/PROKR2 Signaling and Kallmann Syndrome. | Dodé C | Frontiers in endocrinology | 2013 | PMID: 23596439 |
Prioritizing genetic testing in patients with Kallmann syndrome using clinical phenotypes. | Costa-Barbosa FA | The Journal of clinical endocrinology and metabolism | 2013 | PMID: 23533228 |
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 |
SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome. | Hanchate NK | PLoS genetics | 2012 | PMID: 22927827 |
PROKR2 variants in multiple hypopituitarism with pituitary stalk interruption. | Reynaud R | The Journal of clinical endocrinology and metabolism | 2012 | PMID: 22466334 |
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 |
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 |
A comparative phenotypic study of kallmann syndrome patients carrying monoallelic and biallelic mutations in the prokineticin 2 or prokineticin receptor 2 genes. | Sarfati J | The Journal of clinical endocrinology and metabolism | 2010 | PMID: 20022991 |
PROKR2 missense mutations associated with Kallmann syndrome impair receptor signalling activity. | Monnier C | Human molecular genetics | 2009 | PMID: 18826963 |
Mutations in prokineticin 2 and prokineticin receptor 2 genes in human gonadotrophin-releasing hormone deficiency: molecular genetics and clinical spectrum. | Cole LW | The Journal of clinical endocrinology and metabolism | 2008 | PMID: 18559922 |
Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. | Dodé C | PLoS genetics | 2006 | PMID: 17054399 |
Identification of two prokineticin cDNAs: recombinant proteins potently contract gastrointestinal smooth muscle. | Li M | Molecular pharmacology | 2001 | PMID: 11259612 |
The genetic and clinical heterogeneity of gonadotropin-releasing hormone deficiency in the human. | Waldstreicher J | The Journal of clinical endocrinology and metabolism | 1996 | PMID: 8954047 |
Failure of cultured human T-cell lymphoid lines to stimulate in mixed leukocyte culture. | Royston I | Journal of the National Cancer Institute | 1974 | PMID: 4276467 |
click to load more click to collapse |
Text-mined citations for rs144994507 ...
HelpRecord last updated Apr 15, 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.