NM_000141.5(FGFR2):c.1024T>A (p.Cys342Ser) AND Crouzon syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 4, 2022
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:: RCV000014181.29

Allele description [Variation Report for NM_000141.5(FGFR2):c.1024T>A (p.Cys342Ser)]

NM_000141.5(FGFR2):c.1024T>A (p.Cys342Ser)

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.1024T>A (p.Cys342Ser)

HGVS:

NC_000010.11:g.121517379A>T
NG_012449.2:g.86080T>A
NM_000141.5:c.1024T>AMANE SELECT
NM_001144913.1:c.1087+1303T>A
NM_001144914.1:c.749-2060T>A
NM_001144915.2:c.757T>A
NM_001144916.2:c.679T>A
NM_001144917.2:c.939+2600T>A
NM_001144918.2:c.679T>A
NM_001144919.2:c.820+1303T>A
NM_001320654.2:c.340T>A
NM_001320658.2:c.1024T>A
NM_022970.4:c.1087+1303T>A
NM_023029.2:c.757T>A
NP_000132.3:p.Cys342Ser
NP_000132.3:p.Cys342Ser
NP_001138387.1:p.Cys253Ser
NP_001138388.1:p.Cys227Ser
NP_001138390.1:p.Cys227Ser
NP_001307583.1:p.Cys114Ser
NP_001307587.1:p.Cys342Ser
NP_075418.1:p.Cys253Ser
LRG_994t1:c.1024T>A
LRG_994:g.86080T>A
LRG_994p1:p.Cys342Ser
NC_000010.10:g.123276893A>T
NM_000141.4:c.1024T>A
NR_073009.2:n.1460T>A
P21802:p.Cys342Ser
p.[Cys342Ser]

Protein change:

C114S; CYS342SER

Links:

UniProtKB: P21802#VAR_004138; OMIM: 176943.0003; dbSNP: rs121918488

NCBI 1000 Genomes Browser:

rs121918488

Molecular consequence:

NM_001144913.1:c.1087+1303T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001144914.1:c.749-2060T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001144917.2:c.939+2600T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001144919.2:c.820+1303T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_022970.4:c.1087+1303T>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000141.5:c.1024T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001144915.2:c.757T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001144916.2:c.679T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001144918.2:c.679T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001320654.2:c.340T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001320658.2:c.1024T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_023029.2:c.757T>A - missense variant - [Sequence Ontology: SO:0001583]
NR_073009.2:n.1460T>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Crouzon syndrome
Synonyms:: CRANIOFACIAL DYSOSTOSIS, TYPE I; Crouzon craniofacial dysostosis; Crouzon disease; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007405; MeSH: D003394; MedGen: C0010273; Orphanet: 207; OMIM: 123500; Human Phenotype Ontology: HP:0004439

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000034429	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 2000)	germline	literature only	PubMed (4) [See all records that cite these PMIDs] 7987400, 9385368, 10633130, 26362256
SCV002512707	Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 4, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000034429

OMIM

no assertion criteria provided

Pathogenic
(Jan 1, 2000)

germline

literature only

PubMed (4)
[See all records that cite these PMIDs]

SCV002512707

Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 4, 2022)

germline

clinical testing

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

Citations

PubMed

Mutations in the fibroblast growth factor receptor 2 gene cause Crouzon syndrome.

Reardon W, Winter RM, Rutland P, Pulleyn LJ, Jones BM, Malcolm S.

Nat Genet. 1994 Sep;8(1):98-103.

PubMed [citation]

PMID:: 7987400

Jackson-Weiss syndrome: identification of two novel FGFR2 missense mutations shared with Crouzon and Pfeiffer craniosynostotic disorders.

Tartaglia M, Di Rocco C, Lajeunie E, Valeri S, Velardi F, Battaglia PA.

Hum Genet. 1997 Nov;101(1):47-50.

PubMed [citation]

PMID:: 9385368

See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000034429.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (4)

Description

In a sporadic case of Crouzon syndrome (123500), Reardon et al. (1994) found a T-to-A transversion at nucleotide 1036 (the same as that involved in the cys342-to-arg mutation), predicting substitution of serine for cysteine (C342S). This mutation created a new restriction site which was not found in the unaffected parents. This same mutation was found in Jackson-Weiss syndrome (123150) by Tartaglia et al. (1997). The molecular basis for the phenotypic heterogeneity in the face of apparent genetic homogeneity is unclear.

In a patient with an 'extreme' Antley-Bixler phenotype (ABS2; 207410), Reardon et al. (2000) identified the C342S substitution in the FGFR2 gene. The patient had normal female genitalia and a normal steroid profile.

In a 15-year-old girl with Crouzon-like craniosynostosis and 46,XY complete gonadal dysgenesis, Bagheri-Fam et al. (2015) sequenced the candidate gene FGFR2 and identified heterozygosity for the C342S mutation. DNA from her parents was unavailable for study. Whole-exome sequencing to search for potential modifier variants influencing the proband's phenotype revealed single-nucleotide variants or indels in 193 genes. Bagheri-Fam et al. (2015) noted that although none of the changes were located in 63 genes associated with disorders of sex development, the patient did carry novel changes or indels in 35 genes that in mice are expressed in pre-Sertoli cells at the time of sex determination.

#	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 Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein, SCV002512707.1

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

Description

ACMG classification criteria: PS4 strong, PM2 moderate, PM5 moderate, PM6 moderate, PP3 supporting

#	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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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