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.
ClinVar Genomic variation as it relates to human health
NM_023110.3(FGFR1):c.2314C>T (p.Pro772Ser)
Germline
Classification
Help
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.
(14)
Help
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.
Benign/Likely benign
14
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_023110.3(FGFR1):c.2314C>T (p.Pro772Ser)
Variation ID: 194891 Accession: VCV000194891.30
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 8p11.23 8: 38413783 (GRCh38) [ NCBI UCSC ] 8: 38271301 (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 Jun 8, 2016 Sep 29, 2024 Feb 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_023110.3:c.2314C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_075598.2:p.Pro772Ser missense NM_001174063.2:c.2308C>T NP_001167534.1:p.Pro770Ser missense NM_001174064.2:c.2284C>T NP_001167535.1:p.Pro762Ser missense NM_001174065.2:c.2308C>T NP_001167536.1:p.Pro770Ser missense NM_001174066.2:c.2047C>T NP_001167537.1:p.Pro683Ser missense NM_001174067.2:c.2407C>T NP_001167538.1:p.Pro803Ser missense NM_001354367.2:c.2286+135C>T intron variant NM_001354368.2:c.2035C>T NP_001341297.1:p.Pro679Ser missense NM_001354369.2:c.2280+135C>T intron variant NM_001354370.2:c.2019+135C>T intron variant NM_015850.4:c.2308C>T NP_056934.2:p.Pro770Ser missense NM_023105.3:c.2047C>T NP_075593.1:p.Pro683Ser missense NM_023106.3:c.2041C>T NP_075594.1:p.Pro681Ser missense NC_000008.11:g.38413783G>A NC_000008.10:g.38271301G>A NG_007729.1:g.60052C>T LRG_993:g.60052C>T LRG_993t1:c.2314C>T LRG_993p1:p.Pro772Ser P11362:p.Pro772Ser - Protein change
- P772S, P803S, P681S, P683S, P762S, P679S, P770S
- Other names
-
NM_001174063.1(FGFR1):c.2308C>T(p.Pro770Ser)
NM_001174064.1(FGFR1):c.2284C>T(p.Pro762Ser)
NM_001174065.1(FGFR1):c.2308C>T(p.Pro770Ser)
NM_001174066.1(FGFR1):c.2047C>T(p.Pro683Ser)
NM_001174067.1(FGFR1):c.2407C>T(p.Pro803Ser)
NM_015850.3(FGFR1):c.2308C>T(p.Pro770Ser)
NM_023105.2(FGFR1):c.2047C>T(p.Pro683Ser)
NM_023106.2(FGFR1):c.2041C>T(p.Pro681Ser)
NM_023110.2(FGFR1):c.2314C>T(p.Pro772Ser)
- Canonical SPDI
- NC_000008.11:38413782:G:A
-
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.
-
0.00919 (A)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 30x 0.01015
The Genome Aggregation Database (gnomAD) 0.01307
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01386
Exome Aggregation Consortium (ExAC) 0.00382
1000 Genomes Project 0.00919
- Links
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. |
|||
| FGFR1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
998 | 1128 | |
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 (5) |
criteria provided, multiple submitters, no conflicts
|
Mar 25, 2020 | RCV000175365.19 | |
| Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Oct 16, 2023 | RCV000224227.21 | |
| Likely benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV000264893.13 | |
| Likely benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV000316400.13 | |
| Likely benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV000356059.13 | |
| Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
May 31, 2018 | RCV000677340.13 | |
| Benign (1) |
criteria provided, single submitter
|
Feb 1, 2024 | RCV001087665.15 |
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
(Aug 31, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000517335.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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)
|
|
|
Benign
(Apr 25, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: not provided
Allele origin:
germline
|
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000281459.1
First in ClinVar: Jun 08, 2016 Last updated: Jun 08, 2016 |
|
|
|
Likely benign
(May 31, 2018)
|
criteria provided, single submitter
Method: curation
|
Hypogonadotropic hypogonadism 2 with or without anosmia
Affected status: unknown
Allele origin:
unknown
|
SIB Swiss Institute of Bioinformatics
Accession: SCV000803628.1
First in ClinVar: Aug 20, 2018 Last updated: Aug 20, 2018 |
Comment:
This variant is interpreted as a Likely Benign, for hypogonadotropic hypogonadism 2 with or without anosmia, in Autosomal Dominant manner. The following ACMG Tag(s) were … (more)
This variant is interpreted as a Likely Benign, for hypogonadotropic hypogonadism 2 with or without anosmia, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. BS2-Supporting => BS2 downgraded in strength to supporting. (less)
|
|
|
Benign
(Feb 26, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000226838.5
First in ClinVar: Jun 28, 2015 Last updated: Mar 08, 2017 |
Number of individuals with the variant: 2
Sex: mixed
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Craniosynostosis
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000473590.3
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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Hypogonadotropic hypogonadism 2 with or without anosmia
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000473589.3
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)
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Osteoglophonic dysplasia
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000473592.3
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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Trigonocephaly 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000473588.3
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). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Benign
(Mar 25, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital
Accession: SCV001984548.1
First in ClinVar: Oct 30, 2021 Last updated: Oct 30, 2021 |
|
|
|
Benign
(Oct 16, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV001158862.5
First in ClinVar: Feb 10, 2020 Last updated: Feb 20, 2024 |
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Pfeiffer syndrome
Hypogonadotropic hypogonadism 2 with or without anosmia
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000644851.7
First in ClinVar: Dec 26, 2017 Last updated: Feb 28, 2024 |
|
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005223408.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
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: SCV001924260.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927970.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
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Comment:
Comment:
This variant is interpreted as a Likely Benign, for hypogonadotropic hypogonadism 2 with or without anosmia, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. BS2-Supporting => BS2 downgraded in strength to supporting.
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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
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, 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.
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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
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. |
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 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.
Comment:
This variant is interpreted as a Likely Benign, for hypogonadotropic hypogonadism 2 with or without anosmia, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: BS1 => Allele frequency is greater than expected for disorder. BS2-Supporting => BS2 downgraded in strength to supporting.
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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
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, 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.
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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Role of FGFs/FGFRs in skeletal development and bone regeneration. | Du X | Journal of cellular physiology | 2012 | PMID: 22378383 |
| The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism. | Bianco SD | Nature reviews. Endocrinology | 2009 | PMID: 19707180 |
| Kallmann's syndrome: a comparison of the reproductive phenotypes in men carrying KAL1 and FGFR1/KAL2 mutations. | Salenave S | The Journal of clinical endocrinology and metabolism | 2008 | PMID: 18160472 |
| Novel FGFR1 sequence variants in Kallmann syndrome, and genetic evidence that the FGFR1c isoform is required in olfactory bulb and palate morphogenesis. | Dodé C | Human mutation | 2007 | PMID: 17154279 |
| Kallmann syndrome: fibroblast growth factor signaling insufficiency? | Dodé C | Journal of molecular medicine (Berlin, Germany) | 2004 | PMID: 15365636 |
| Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. | Dodé C | Nature genetics | 2003 | PMID: 12627230 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=FGFR1 | - | - | - | - |
Text-mined citations for rs56234888 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record 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.