ClinVar Genomic variation as it relates to human health
NM_000142.4(FGFR3):c.[1130T>G;1138G>A]
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
NM_000142.4(FGFR3):c.[1130T>G;1138G>A]
- Other names
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FGFR3, GLY380ARG AND LEU377ARG
- Functional consequence
- -
- Links
- ClinGen: CA357254
- OMIM: 134934.0027
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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| FGFR3 | No evidence available | No evidence available |
GRCh38 GRCh37 |
984 | 1134 | |
Conditions - Germline
| Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Pathogenic (1) |
no assertion criteria provided
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Feb 1, 2006 | RCV000017763.38 |
Submissions - Germline
| Classification
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The submitted germline classification for each SCV record. (Last evaluated) |
Review status
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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
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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
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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
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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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|---|---|---|---|---|---|
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Pathogenic
(Feb 01, 2006)
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no assertion criteria provided
Method: literature only
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ACHONDROPLASIA
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000038041.2
First in ClinVar: Apr 04, 2013 Last updated: Jun 09, 2024 |
Comment on evidence:
In a Dutch infant with a severe form of achondroplasia (ACH; 100800), Rump et al. (2006) identified 2 de novo mutations in the FGFR3 gene … (more)
In a Dutch infant with a severe form of achondroplasia (ACH; 100800), Rump et al. (2006) identified 2 de novo mutations in the FGFR3 gene on the same allele. One was the common G380R mutation (134934.0001), and the other was a 1130T-G transversion, resulting in a leu377-to-arg (L377R) substitution within the transmembrane domain. Allele-specific PCR analysis confirmed that the 2 mutations were in cis. From birth, the child had severe respiratory difficulties with multiple hypoxic episodes due to a combination of upper airway obstruction, pulmonary hypoplasia, and cervicomedullary compression. He eventually became ventilator dependent and died at age 4 months. (less)
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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
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Achondroplasia. | Adam MP | - | 2023 | PMID: 20301331 |
| Molecular diagnosis for 55 fetuses with skeletal dysplasias by whole-exome sequencing: A retrospective cohort study. | Zhang L | Clinical genetics | 2021 | PMID: 33942288 |
| Clinical application of medical exome sequencing for prenatal diagnosis of fetal structural anomalies. | Chen M | European journal of obstetrics, gynecology, and reproductive biology | 2020 | PMID: 32502767 |
| Rapid prenatal diagnosis of skeletal dysplasia using medical trio exome sequencing: Benefit for prenatal counseling and pregnancy management. | Han J | Prenatal diagnosis | 2020 | PMID: 31994750 |
| Hypochondroplasia. | Adam MP | - | 2020 | PMID: 20301650 |
| Prenatal diagnosis of fetal skeletal dysplasia using targeted next-generation sequencing: an analysis of 30 cases. | Liu Y | Diagnostic pathology | 2019 | PMID: 31299979 |
| Genetic Analysis in Fetal Skeletal Dysplasias by Trio Whole-Exome Sequencing. | Yang K | BioMed research international | 2019 | PMID: 31218223 |
| Non-invasive prenatal sequencing for multiple Mendelian monogenic disorders using circulating cell-free fetal DNA. | Zhang J | Nature medicine | 2019 | PMID: 30692697 |
| Genetic Evaluation of 114 Chinese Short Stature Children in the Next Generation Era: a Single Center Study. | Huang Z | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2018 | PMID: 30138938 |
| Further delineation of achondroplasia-hypochondroplasia complex with long-term survival. | González-Del Angel A | American journal of medical genetics. Part A | 2018 | PMID: 29681095 |
| Novel and Recurrent Mutations in the FGFR3 Gene and Double Heterozygosity Cases in a Cohort of Brazilian Patients with Skeletal Dysplasia. | Gomes MES | Molecular syndromology | 2018 | PMID: 29593476 |
| [Rapid detection of hot spot mutations of FGFR3 gene with PCR-high resolution melting assay]. | Li S | Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics | 2017 | PMID: 28777845 |
| Knock-in human FGFR3 achondroplasia mutation as a mouse model for human skeletal dysplasia. | Lee YC | Scientific reports | 2017 | PMID: 28230213 |
| Association of achondroplasia with sagittal synostosis and scaphocephaly in two patients, an underestimated condition? | Accogli A | American journal of medical genetics. Part A | 2015 | PMID: 25691418 |
| FGFR3 mutation frequency in 324 cases from the International Skeletal Dysplasia Registry. | Xue Y | Molecular genetics & genomic medicine | 2014 | DOI: 10.1002/mgg3.96 |
| FGFR3 mutation frequency in 324 cases from the International Skeletal Dysplasia Registry. | Xue Y | Molecular genetics & genomic medicine | 2014 | PMID: 25614871 |
| A novel homozygous mutation in FGFR3 causes tall stature, severe lateral tibial deviation, scoliosis, hearing impairment, camptodactyly, and arachnodactyly. | Makrythanasis P | Human mutation | 2014 | PMID: 24864036 |
| Structure of FGFR3 transmembrane domain dimer: implications for signaling and human pathologies. | Bocharov EV | Structure (London, England : 1993) | 2013 | PMID: 24120763 |
| Direct assessment of the effect of the Gly380Arg achondroplasia mutation on FGFR3 dimerization using quantitative imaging FRET. | Placone J | PloS one | 2012 | PMID: 23056398 |
| Sixteen years and counting: the current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias. | Foldynova-Trantirkova S | Human mutation | 2012 | PMID: 22045636 |
| Achondroplasia with synostosis of multiple sutures. | Georgoulis G | American journal of medical genetics. Part A | 2011 | PMID: 21739570 |
| FGFR3 heterodimerization in achondroplasia, the most common form of human dwarfism. | He L | The Journal of biological chemistry | 2011 | PMID: 21324899 |
| Physical basis behind achondroplasia, the most common form of human dwarfism. | He L | The Journal of biological chemistry | 2010 | PMID: 20624921 |
| Germline mosaicism in achondroplasia detected in sperm DNA of the father of three affected sibs. | Natacci F | American journal of medical genetics. Part A | 2008 | PMID: 18266238 |
| FGFR3 intracellular mutations induce tyrosine phosphorylation in the Golgi and defective glycosylation. | Gibbs L | Biochimica et biophysica acta | 2007 | PMID: 17320202 |
| A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome. | Toydemir RM | American journal of human genetics | 2006 | PMID: 17033969 |
| Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi. | Hafner C | The Journal of clinical investigation | 2006 | PMID: 16841094 |
| Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm. | Wyrobek AJ | Proceedings of the National Academy of Sciences of the United States of America | 2006 | PMID: 16766665 |
| Severe complications in a child with achondroplasia and two FGFR3 mutations on the same allele. | Rump P | American journal of medical genetics. Part A | 2006 | PMID: 16411219 |
| Severe complications in a child with achondroplasia and two FGFR3 mutations on the same allele. | Rump P | American journal of medical genetics. Part A | 2006 | PMID: 16411219 |
| Acanthosis nigricans in a boy with achondroplasia due to the classical Gly380Arg mutation in FGFR3. | Van Esch H | Genetic counseling (Geneva, Switzerland) | 2004 | PMID: 15517832 |
| Achondroplasia with the FGFR3 1138g-->a (G380R) mutation in two sibs sharing a 4p haplotype derived from their unaffected father. | Sobetzko D | Journal of medical genetics | 2000 | PMID: 11186940 |
| Germline and somatic mosaicism in achondroplasia. | Henderson S | Journal of medical genetics | 2000 | PMID: 11186939 |
| Prenatal DNA diagnosis of a single-gene disorder from maternal plasma. | Saito H | Lancet (London, England) | 2000 | PMID: 11030304 |
| Achondroplasia in diverse Jewish and Arab populations in Israel: clinical and molecular characterization. | Falik-Zaccai TC | The Israel Medical Association journal : IMAJ | 2000 | PMID: 10979354 |
| Restrained chondrocyte proliferation and maturation with abnormal growth plate vascularization and ossification in human FGFR-3(G380R) transgenic mice. | Segev O | Human molecular genetics | 2000 | PMID: 10607835 |
| Exclusive paternal origin of new mutations in Apert syndrome. | Moloney DM | Nature genetics | 1996 | PMID: 8673103 |
| Achondroplasia is defined by recurrent G380R mutations of FGFR3. | Bellus GA | American journal of human genetics | 1995 | PMID: 7847369 |
| A common FGFR3 gene mutation is present in achondroplasia but not in hypochondroplasia. | Stoilov I | American journal of medical genetics | 1995 | PMID: 7702086 |
| A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. | Bellus GA | Nature genetics | 1995 | PMID: 7670477 |
| Mutations of the fibroblast growth factor receptor-3 gene in one familial and six sporadic cases of achondroplasia in Japanese patients. | Ikegawa S | Human genetics | 1995 | PMID: 7649548 |
| Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. | Rousseau F | Nature | 1994 | PMID: 8078586 |
| Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. | Shiang R | Cell | 1994 | PMID: 7913883 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=FGFR3 | - | - | - | - |
| Szabo, J., Bellus, G. A., Kaitila, I., Francomano, C. A. Fibroblast growth factor receptor 3 (FGFR3) mutations in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. (Abstract) Am. J. Hum. Genet. 59 (suppl.): A287-only, 1996. | - | - | - | - |
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Text-mined citations for this variant ...
HelpRecord last updated Nov 25, 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.