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

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:
RCV003987651.2

Allele description [Variation Report for NM_000141.5(FGFR2):c.755C>T (p.Ser252Leu)]

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

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004804229Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Uncertain significance
(Jan 8, 2024)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 10, 2024