NM_000141.5(FGFR2):c.755_756delinsTT (p.Ser252Phe) AND Acrocephalosyndactyly type I

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Sep 17, 2016
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:: RCV000014201.31

Allele description [Variation Report for NM_000141.5(FGFR2):c.755_756delinsTT (p.Ser252Phe)]

NM_000141.5(FGFR2):c.755_756delinsTT (p.Ser252Phe)

Gene:

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

Variant type:

Indel

Cytogenetic location:

10q26.13

Genomic location:

Preferred name:

NM_000141.5(FGFR2):c.755_756delinsTT (p.Ser252Phe)

HGVS:

NC_000010.11:g.121520162_121520163delinsAA
NG_012449.2:g.83296_83297delinsTT
NM_000141.5:c.755_756delinsTTMANE SELECT
NM_001144913.1:c.755_756delinsTT
NM_001144914.1:c.749-4844_749-4843delinsTT
NM_001144915.2:c.488_489delinsTT
NM_001144916.2:c.410_411delinsTT
NM_001144917.2:c.755_756delinsTT
NM_001144918.2:c.410_411delinsTT
NM_001144919.2:c.488_489delinsTT
NM_001320654.2:c.71_72delinsTT
NM_001320658.2:c.755_756delinsTT
NM_022969.1:c.755_756delCGinsTT
NM_022970.4:c.755_756delCGinsTT
NM_023029.2:c.488_489delinsTT
NP_000132.3:p.Ser252Phe
NP_000132.3:p.Ser252Phe
NP_001138385.1:p.Ser252Phe
NP_001138387.1:p.Ser163Phe
NP_001138388.1:p.Ser137Phe
NP_001138389.1:p.Ser252Phe
NP_001138390.1:p.Ser137Phe
NP_001138391.1:p.Ser163Phe
NP_001307583.1:p.Ser24Phe
NP_001307587.1:p.Ser252Phe
NP_075258.1:p.Ser252Phe
NP_075259.4:p.Ser252Phe
NP_075259.4:p.Ser252Phe
NP_075418.1:p.Ser163Phe
LRG_994t1:c.755_756delCGinsTT
LRG_994t2:c.755_756delinsTT
LRG_994:g.83296_83297delinsTT
LRG_994p1:p.Ser252Phe
LRG_994p2:p.Ser252Phe
NC_000010.10:g.123279676_123279677delinsAA
NM_000141.4:c.755_756delCGinsTT
NM_000141.4:c.755_756delCGinsTT
NM_022970.3:c.755_756delinsTT
NR_073009.2:n.1043_1044delinsTT
p.[Ser252Phe]

Protein change:

S137F; SER252PHE

Links:

OMIM: 176943.0017; dbSNP: rs121918498

NCBI 1000 Genomes Browser:

rs121918498

Molecular consequence:

NM_001144914.1:c.749-4844_749-4843delinsTT - intron variant - [Sequence Ontology: SO:0001627]
NM_000141.5:c.755_756delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001144913.1:c.755_756delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001144915.2:c.488_489delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001144916.2:c.410_411delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001144917.2:c.755_756delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001144918.2:c.410_411delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001144919.2:c.488_489delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001320654.2:c.71_72delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001320658.2:c.755_756delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_022969.1:c.755_756delCGinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_022970.4:c.755_756delCGinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_023029.2:c.488_489delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NR_073009.2:n.1043_1044delinsTT - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Acrocephalosyndactyly type I (ACS1)
Synonyms:: Apert syndrome; Acrocephalo-syndactyly type 1; ACS 1; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007041; MedGen: C0001193; Orphanet: 87; OMIM: 101200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000034449	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 1999)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 9002682, 10067911
SCV000328368	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	criteria provided, single submitter (DGD Variant Analysis Guidelines)	Likely pathogenic (Sep 17, 2016)	germline	clinical testing	Citation Link,
SCV000929989	GeneReviews	no classification provided	not provided	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000034449

OMIM

no assertion criteria provided

Pathogenic
(Mar 1, 1999)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000328368

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

criteria provided, single submitter

(DGD Variant Analysis Guidelines)

Likely pathogenic
(Sep 17, 2016)

germline

clinical testing

Citation Link,

SCV000929989

GeneReviews

no classification provided

not provided

germline

literature only

PubMed (1)
[See all records that cite this PMID]

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	literature only
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genotype-phenotype correlation for nucleotide substitutions in the IgII-IgIII linker of FGFR2.

Oldridge M, Lunt PW, Zackai EH, McDonald-McGinn DM, Muenke M, Moloney DM, Twigg SR, Heath JK, Howard TD, Hoganson G, Gagnon DM, Jabs EW, Wilkie AO.

Hum Mol Genet. 1997 Jan;6(1):137-43.

PubMed [citation]

PMID:: 9002682

Clinical variability in patients with Apert's syndrome.

Lajeunie E, Cameron R, El Ghouzzi V, de Parseval N, Journeau P, Gonzales M, Delezoide AL, Bonaventure J, Le Merrer M, Renier D.

J Neurosurg. 1999 Mar;90(3):443-7.

PubMed [citation]

PMID:: 10067911

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000034449.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a patient with Apert syndrome (101200), Oldridge et al. (1997) identified a CG-to-TT change in the FGFR2 gene, resulting in a ser252-to-phe (S252F) substitution. This was said to be the first noncanonical mutation to be identified in Apert syndrome, its rarity being explained by the requirement for 2 residues of the serine codon to be mutated.

Lajeunie et al. (1999) identified the S252F substitution in a fetus with Apert syndrome.

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

From Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia, SCV000328368.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

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

From GeneReviews, SCV000929989.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

#	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: May 7, 2024

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