ClinVar Genomic variation as it relates to human health
NM_000141.5(FGFR2):c.799T>C (p.Ser267Pro)
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_000141.5(FGFR2):c.799T>C (p.Ser267Pro)
Variation ID: 13290 Accession: VCV000013290.15
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q26.13 10: 121520119 (GRCh38) [ NCBI UCSC ] 10: 123279633 (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 Sep 9, 2016 Feb 14, 2024 Sep 8, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000141.5:c.799T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000132.3:p.Ser267Pro missense NM_022970.4:c.799T>C MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_075259.4:p.Ser267Pro missense NM_001144913.1:c.799T>C NP_001138385.1:p.Ser267Pro missense NM_001144914.1:c.749-4800T>C intron variant NM_001144915.2:c.532T>C NP_001138387.1:p.Ser178Pro missense NM_001144916.2:c.454T>C NP_001138388.1:p.Ser152Pro missense NM_001144917.2:c.799T>C NP_001138389.1:p.Ser267Pro missense NM_001144918.2:c.454T>C NP_001138390.1:p.Ser152Pro missense NM_001144919.2:c.532T>C NP_001138391.1:p.Ser178Pro missense NM_001320654.2:c.115T>C NP_001307583.1:p.Ser39Pro missense NM_001320658.2:c.799T>C NP_001307587.1:p.Ser267Pro missense NM_022969.1:c.799T>C NP_075258.1:p.Ser267Pro missense NM_023029.2:c.532T>C NP_075418.1:p.Ser178Pro missense NR_073009.2:n.1087T>C non-coding transcript variant NC_000010.11:g.121520119A>G NC_000010.10:g.123279633A>G NG_012449.2:g.83340T>C LRG_994:g.83340T>C LRG_994t1:c.799T>C LRG_994p1:p.Ser267Pro LRG_994t2:c.799T>C LRG_994p2:p.Ser267Pro P21802:p.Ser267Pro - Protein change
- S267P, S152P, S178P, S39P
- Other names
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- Canonical SPDI
- NC_000010.11:121520118:A:G
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
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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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FGFR2 | - | - |
GRCh38 GRCh37 |
735 | 787 |
Conditions - Germline
Condition
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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
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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. |
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Pathogenic (2) |
criteria provided, single submitter
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Sep 17, 2016 | RCV000014213.34 | |
Pathogenic (2) |
criteria provided, single submitter
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Jun 6, 2019 | RCV000408850.13 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 8, 2023 | RCV000435703.7 | |
Pathogenic (1) |
criteria provided, single submitter
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Dec 6, 2022 | RCV000690962.16 | |
Pathogenic (1) |
no assertion criteria provided
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May 1, 2001 | RCV002508123.8 |
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
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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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Pathogenic
(Sep 17, 2016)
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criteria provided, single submitter
Method: clinical testing
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Pfeiffer syndrome
Affected status: yes
Allele origin:
germline
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Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000328370.2
First in ClinVar: Sep 09, 2016 Last updated: Mar 04, 2023
Comment:
Clinical Testing
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Number of individuals with the variant: 2
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Pathogenic
(Jun 06, 2019)
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criteria provided, single submitter
Method: clinical testing
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Crouzon syndrome
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV001149777.1
First in ClinVar: Feb 03, 2020 Last updated: Feb 03, 2020 |
Sex: female
Tissue: blood
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Pathogenic
(Sep 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000516004.6
First in ClinVar: Mar 08, 2017 Last updated: Sep 14, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23348274, 26224133, 23754559, 25759927, 11325814, 10394936, 11781872, 7655462, 9700203, 31318164, 26003532, 29230096, 29104507, 26152202, 28476232, 27002187, 26460964, 29928180, 35253369) (less)
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Pathogenic
(Dec 06, 2022)
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criteria provided, single submitter
Method: clinical testing
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FGFR2-related craniosynostosis
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000818693.7
First in ClinVar: Oct 10, 2018 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects FGFR2 function (PMID: 9700203). Advanced modeling … (more)
For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects FGFR2 function (PMID: 9700203). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FGFR2 protein function. ClinVar contains an entry for this variant (Variation ID: 13290). This variant is also known as 811T>C. This missense change has been observed in individual(s) with Crouzon syndrome and/or Pfeiffer syndrome (PMID: 7655462, 10394936, 11781872, 16418739, 23348274, 24127277, 25759927). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 267 of the FGFR2 protein (p.Ser267Pro). (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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Crouzon syndrome
Affected status: yes
Allele origin:
germline
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Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare
Accession: SCV000484911.1
First in ClinVar: Dec 18, 2016 Last updated: Dec 18, 2016 |
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Pathogenic
(May 01, 2001)
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no assertion criteria provided
Method: literature only
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PFEIFFER SYNDROME
Affected status: not provided
Allele origin:
unknown
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OMIM
Accession: SCV000034461.2
First in ClinVar: Apr 04, 2013 Last updated: Sep 09, 2016 |
Comment on evidence:
Cornejo-Roldan et al. (1999) described a T-to-C transition at nucleotide 799 of the FGFR2 gene, resulting in a ser267-to-pro de novo mutation in each of … (more)
Cornejo-Roldan et al. (1999) described a T-to-C transition at nucleotide 799 of the FGFR2 gene, resulting in a ser267-to-pro de novo mutation in each of 2 sporadic cases of Pfeiffer syndrome (101600). Jang et al. (2001) found the same change as a somatic mutation in gastric cancer (137215). Thus, a heterozygous somatic mutation identical to a germinal activating mutation in FGFR2 in a craniosynostosis syndrome resulted in cancer. (less)
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Pathogenic
(May 01, 2001)
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no assertion criteria provided
Method: literature only
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GASTRIC CANCER, SOMATIC
Affected status: not provided
Allele origin:
somatic
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OMIM
Accession: SCV000034462.2
First in ClinVar: Apr 04, 2013 Last updated: Sep 09, 2016 |
Comment on evidence:
Cornejo-Roldan et al. (1999) described a T-to-C transition at nucleotide 799 of the FGFR2 gene, resulting in a ser267-to-pro de novo mutation in each of … (more)
Cornejo-Roldan et al. (1999) described a T-to-C transition at nucleotide 799 of the FGFR2 gene, resulting in a ser267-to-pro de novo mutation in each of 2 sporadic cases of Pfeiffer syndrome (101600). Jang et al. (2001) found the same change as a somatic mutation in gastric cancer (137215). Thus, a heterozygous somatic mutation identical to a germinal activating mutation in FGFR2 in a craniosynostosis syndrome resulted in cancer. (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
HelpTitle | Author | Journal | Year | Link |
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Genotype and clinical care correlations in craniosynostosis: findings from a cohort of 630 Australian and New Zealand patients. | Roscioli T | American journal of medical genetics. Part C, Seminars in medical genetics | 2013 | PMID: 24127277 |
FGFR1 and FGFR2 mutations in Pfeiffer syndrome. | Chokdeemboon C | The Journal of craniofacial surgery | 2013 | PMID: 23348274 |
Genomic screening of fibroblast growth-factor receptor 2 reveals a wide spectrum of mutations in patients with syndromic craniosynostosis. | Kan SH | American journal of human genetics | 2002 | PMID: 11781872 |
Mutations in fibroblast growth factor receptor 2 and fibroblast growth factor receptor 3 genes associated with human gastric and colorectal cancers. | Jang JH | Cancer research | 2001 | PMID: 11325814 |
Analysis of the mutational spectrum of the FGFR2 gene in Pfeiffer syndrome. | Cornejo-Roldan LR | Human genetics | 1999 | PMID: 10394936 |
Apert syndrome mutations in fibroblast growth factor receptor 2 exhibit increased affinity for FGF ligand. | Anderson J | Human molecular genetics | 1998 | PMID: 9700203 |
Mutations in the third immunoglobulin domain of the fibroblast growth factor receptor-2 gene in Crouzon syndrome. | Oldridge M | Human molecular genetics | 1995 | PMID: 7655462 |
Text-mined citations for rs121918505 ...
HelpRecord last updated Jun 10, 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.