ClinVar Genomic variation as it relates to human health
NM_000141.5(FGFR2):c.826T>G (p.Phe276Val)
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.826T>G (p.Phe276Val)
Variation ID: 374809 Accession: VCV000374809.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q26.13 10: 121520092 (GRCh38) [ NCBI UCSC ] 10: 123279606 (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 Jan 20, 2017 Feb 14, 2024 Nov 27, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000141.5:c.826T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000132.3:p.Phe276Val missense NM_022970.4:c.826T>G MANE Plus Clinical Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_075259.4:p.Phe276Val missense NM_001144913.1:c.826T>G NP_001138385.1:p.Phe276Val missense NM_001144914.1:c.749-4773T>G intron variant NM_001144915.2:c.559T>G NP_001138387.1:p.Phe187Val missense NM_001144916.2:c.481T>G NP_001138388.1:p.Phe161Val missense NM_001144917.2:c.826T>G NP_001138389.1:p.Phe276Val missense NM_001144918.2:c.481T>G NP_001138390.1:p.Phe161Val missense NM_001144919.2:c.559T>G NP_001138391.1:p.Phe187Val missense NM_001320654.2:c.142T>G NP_001307583.1:p.Phe48Val missense NM_001320658.2:c.826T>G NP_001307587.1:p.Phe276Val missense NM_022969.1:c.826T>G NP_075258.1:p.Phe276Val missense NM_023029.2:c.559T>G NP_075418.1:p.Phe187Val missense NR_073009.2:n.1114T>G non-coding transcript variant NC_000010.11:g.121520092A>C NC_000010.10:g.123279606A>C NG_012449.2:g.83367T>G LRG_994:g.83367T>G LRG_994t1:c.826T>G LRG_994p1:p.Phe276Val LRG_994t2:c.826T>G LRG_994p2:p.Phe276Val - Protein change
- F276V, F161V, F187V, F48V
- Other names
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- Canonical SPDI
- NC_000010.11:121520091:A:C
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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
Help
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 |
731 | 784 |
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
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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 (1) |
criteria provided, single submitter
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Sep 17, 2016 | RCV000415486.9 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 27, 2023 | RCV000655413.13 | |
Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Jun 1, 2022 | RCV001723974.13 |
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
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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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Crouzon syndrome
Affected status: yes
Allele origin:
germline
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Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000328371.2
First in ClinVar: Jan 20, 2017 Last updated: Mar 04, 2023
Comment:
Clinical Testing
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Number of individuals with the variant: 4
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Likely pathogenic
(Jun 01, 2022)
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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: SCV002525279.2
First in ClinVar: Jun 03, 2022 Last updated: Mar 04, 2023 |
Comment:
Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated … (more)
Not observed in large population cohorts (gnomAD); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 24656465, 23754559, 24127277, 9521581, 22355256, 11173845, 11781872, 10633130, 10394936, 17693524, 10541159, 25271085, 35372644, 32178948) (less)
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Pathogenic
(Nov 03, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002011025.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Pathogenic
(Nov 27, 2023)
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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: SCV000777343.6
First in ClinVar: May 28, 2018 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 276 of the FGFR2 protein (p.Phe276Val). … (more)
This sequence change replaces phenylalanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 276 of the FGFR2 protein (p.Phe276Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with craniosynostosis conditions, including Crouzon syndrome and Pfeiffer syndrome (PMID: 9521581, 10394936, 10633130, 11781872, 24127277, 24656465). ClinVar contains an entry for this variant (Variation ID: 374809). 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) performed at Invitae indicates that this missense variant is expected to disrupt FGFR2 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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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: SCV001959120.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001968454.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
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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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Clinicogenetic study of Turkish patients with syndromic craniosynostosis and literature review. | Nur BG | Pediatric neurology | 2014 | PMID: 24656465 |
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 |
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 |
Evidence for digenic inheritance in some cases of Antley-Bixler syndrome? | Reardon W | Journal of medical genetics | 2000 | PMID: 10633130 |
Analysis of the mutational spectrum of the FGFR2 gene in Pfeiffer syndrome. | Cornejo-Roldan LR | Human genetics | 1999 | PMID: 10394936 |
The mutations in FGFR2-associated craniosynostoses are clustered in five structural elements of immunoglobulin-like domain III of the receptor. | Steinberger D | Human genetics | 1998 | PMID: 9521581 |
Text-mined citations for rs1057519036 ...
HelpRecord last updated May 01, 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.