NM_000141.5(FGFR2):c.755C>T (p.Ser252Leu) AND not specified

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 8, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003987651.1

Allele description

NM_000141.5(FGFR2):c.755C>T (p.Ser252Leu)

Gene:

FGFR2:fibroblast growth factor receptor 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q26.13

Genomic location:

Preferred name:

NM_000141.5(FGFR2):c.755C>T (p.Ser252Leu)

Other names:

NM_000141.4:c.755C>T(p.Ser252Leu); NM_001144913.1:c.755C>T(p.Ser252Leu); NM_001144915.1:c.488C>T(p.Ser163Leu); NM_001144916.1:c.410C>T(p.Ser137Leu); NM_001144917.1:c.755C>T(p.Ser252Leu); NM_001144918.1:c.410C>T(p.Ser137Leu); NM_001144919.1:c.488C>T(p.Ser163Leu); NM_022970.3:c.755C>T(p.Ser252Leu); NM_023029.2:c.488C>T(p.Ser163Leu)

HGVS:

NC_000010.11:g.121520163G>A
NG_012449.2:g.83296C>T
NM_000141.5:c.755C>TMANE SELECT
NM_001144913.1:c.755C>T
NM_001144914.1:c.749-4844C>T
NM_001144915.2:c.488C>T
NM_001144916.2:c.410C>T
NM_001144917.2:c.755C>T
NM_001144918.2:c.410C>T
NM_001144919.2:c.488C>T
NM_001320654.2:c.71C>T
NM_001320658.2:c.755C>T
NM_022969.1:c.755C>T
NM_022970.4:c.755C>T
NM_023029.2:c.488C>T
NP_000132.3:p.Ser252Leu
NP_000132.3:p.Ser252Leu
NP_001138385.1:p.Ser252Leu
NP_001138387.1:p.Ser163Leu
NP_001138388.1:p.Ser137Leu
NP_001138389.1:p.Ser252Leu
NP_001138390.1:p.Ser137Leu
NP_001138391.1:p.Ser163Leu
NP_001307583.1:p.Ser24Leu
NP_001307587.1:p.Ser252Leu
NP_075258.1:p.Ser252Leu
NP_075259.4:p.Ser252Leu
NP_075259.4:p.Ser252Leu
NP_075418.1:p.Ser163Leu
LRG_994t1:c.755C>T
LRG_994t2:c.755C>T
LRG_994:g.83296C>T
LRG_994p1:p.Ser252Leu
LRG_994p2:p.Ser252Leu
NC_000010.10:g.123279677G>A
NM_000141.4:c.755C>T
NM_000141.5:c.755C>T
NM_022970.3:c.755C>T
NR_073009.2:n.1043C>T

Protein change:

S137L

Links:

dbSNP: rs79184941

NCBI 1000 Genomes Browser:

rs79184941

Molecular consequence:

NM_001144914.1:c.749-4844C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000141.5:c.755C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001144913.1:c.755C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001144915.2:c.488C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001144916.2:c.410C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001144917.2:c.755C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001144918.2:c.410C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001144919.2:c.488C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001320654.2:c.71C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001320658.2:c.755C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_022969.1:c.755C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_022970.4:c.755C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_023029.2:c.488C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_073009.2:n.1043C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004804229	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jan 8, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 9700203, 15282208, 9002682, 27683237, 11711827, 12357470 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004804229

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jan 8, 2024)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Apert syndrome mutations in fibroblast growth factor receptor 2 exhibit increased affinity for FGF ligand.

Anderson J, Burns HD, Enriquez-Harris P, Wilkie AO, Heath JK.

Hum Mol Genet. 1998 Sep;7(9):1475-83.

PubMed [citation]

PMID:: 9700203

Biochemical analysis of pathogenic ligand-dependent FGFR2 mutations suggests distinct pathophysiological mechanisms for craniofacial and limb abnormalities.

Ibrahimi OA, Zhang F, Eliseenkova AV, Itoh N, Linhardt RJ, Mohammadi M.

Hum Mol Genet. 2004 Oct 1;13(19):2313-24. Epub 2004 Jul 28.

PubMed [citation]

PMID:: 15282208
PMCID:: PMC4140565

See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004804229.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Variant summary: FGFR2 c.755C>T (p.Ser252Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. c.755C>T has been reported in the literature in two independent families affected with Crouzon syndrome and the variant was present in both affected individuals as well as clinically normal family members (examples: Oldridge_1997, Oshini_2017). Additionally, this variant was seen in cis with a second pathogenic variant in a mother and her daughter affected with syndactyly (Wilkie_2002). At least one publication reports experimental evidence that FGFR2 mutant Ser252Leu exhibited kinetic behavior identical to wild-type (Anderson_1998). These data suggest a benign role for this variant however, other variants affecting this residue have been classified pathogenic/likely pathogenic in ClinVar (CV IDs: 13272, 13279). ClinVar contains an entry for this variant (Variation ID: 549484). The following publications have been ascertained in the context of this evaluation (PMID: 9002682, 9700203, 15282208, 11711827, 27683237, 12357470). Based on the evidence outlined above, the variant was classified as uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 16, 2024

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