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

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Jun 30, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000664049.4

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)

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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Mus musculus dystrobrevin alpha (Dtna), transcript variant 1, mRNA
Mus musculus dystrobrevin alpha (Dtna), transcript variant 1, mRNA
gi|551894828|ref|NM_001285807.1|

Nucleotide
Mus musculus RAB4A, member RAS oncogene family (Rab4a), mRNA
Mus musculus RAB4A, member RAS oncogene family (Rab4a), mRNA
gi|171184401|ref|NM_009003.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000787470	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Apr 16, 2018)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 9002682, 25741868
SCV001138181	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Likely benign (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV001430659	Johns Hopkins Genomics, Johns Hopkins University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Jun 30, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15282208, 9002682, 9700203, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000787470

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Apr 16, 2018)

germline

curation

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

SCV001138181

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Likely benign
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV001430659

Johns Hopkins Genomics, Johns Hopkins University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Jun 30, 2020)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

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

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

See all PubMed Citations (4)

Details of each submission

From SIB Swiss Institute of Bioinformatics, SCV000787470.1

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

Description

This variant is interpreted as a Benign, for Crouzon syndrome, Autosomal Dominant inheritance. The following ACMG Tag(s) were applied: BS4 => Lack of segregation in affected members of a family (PMID:9002682). BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age (PMID:9002682).

#	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

From Mendelics, SCV001138181.1

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

From Johns Hopkins Genomics, Johns Hopkins University, SCV001430659.1

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

#	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: Oct 26, 2024

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