NM_000141.5(FGFR2):c.962A>C (p.Asp321Ala) AND Pfeiffer syndrome

Germline classification:: Pathogenic (2 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:: RCV000014227.28

Allele description [Variation Report for NM_000141.5(FGFR2):c.962A>C (p.Asp321Ala)]

NM_000141.5(FGFR2):c.962A>C (p.Asp321Ala)

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.962A>C (p.Asp321Ala)

HGVS:

NC_000010.11:g.121517441T>G
NG_012449.2:g.86018A>C
NM_000141.5:c.962A>CMANE SELECT
NM_001144913.1:c.1087+1241A>C
NM_001144914.1:c.749-2122A>C
NM_001144915.2:c.695A>C
NM_001144916.2:c.617A>C
NM_001144917.2:c.939+2538A>C
NM_001144918.2:c.617A>C
NM_001144919.2:c.820+1241A>C
NM_001320654.2:c.278A>C
NM_001320658.2:c.962A>C
NM_022970.4:c.1087+1241A>C
NM_023029.2:c.695A>C
NP_000132.3:p.Asp321Ala
NP_000132.3:p.Asp321Ala
NP_001138387.1:p.Asp232Ala
NP_001138388.1:p.Asp206Ala
NP_001138390.1:p.Asp206Ala
NP_001307583.1:p.Asp93Ala
NP_001307587.1:p.Asp321Ala
NP_075418.1:p.Asp232Ala
LRG_994t1:c.962A>C
LRG_994:g.86018A>C
LRG_994p1:p.Asp321Ala
NC_000010.10:g.123276955T>G
NM_000141.4:c.962A>C
NR_073009.2:n.1398A>C
P21802:p.Asp321Ala
p.[Asp321Ala]

Protein change:

D206A; ASP321ALA

Links:

UniProtKB: P21802#VAR_004129; OMIM: 176943.0039; dbSNP: rs121918510

NCBI 1000 Genomes Browser:

rs121918510

Molecular consequence:

NM_001144913.1:c.1087+1241A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001144914.1:c.749-2122A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001144917.2:c.939+2538A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001144919.2:c.820+1241A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_022970.4:c.1087+1241A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000141.5:c.962A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001144915.2:c.695A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001144916.2:c.617A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001144918.2:c.617A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001320654.2:c.278A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001320658.2:c.962A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_023029.2:c.695A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_073009.2:n.1398A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Pfeiffer syndrome (ACS5)
Synonyms:: ACS V; Pfeiffer type acrocephalosyndactyly; Acrocephalosyndactyly, type 5
Identifiers:: MONDO: MONDO:0007043; MedGen: C0220658; Orphanet: 710; OMIM: 101600

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kremen protein 1 isoform 2 precursor [Homo sapiens]
kremen protein 1 isoform 2 precursor [Homo sapiens]
gi|24041012|ref|NP_114434.3|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000034475	OMIM	no assertion criteria provided	Pathogenic (Oct 1, 2004)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 9586546, 7719333, 15282208
SCV000328383	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	criteria provided, single submitter (DGD Variant Analysis Guidelines)	Pathogenic (Sep 17, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000034475

OMIM

no assertion criteria provided

Pathogenic
(Oct 1, 2004)

germline

literature only

PubMed (3)
[See all records that cite these PMIDs]

SCV000328383

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

criteria provided, single submitter

(DGD Variant Analysis Guidelines)

Pathogenic
(Sep 17, 2016)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
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

Mutations in fibroblast growth factor receptor 2 gene and craniosynostotic syndromes in Japanese children.

Nagase T, Nagase M, Hirose S, Ohmori K.

J Craniofac Surg. 1998 Mar;9(2):162-70.

PubMed [citation]

PMID:: 9586546

FGFR2 mutations in Pfeiffer syndrome.

Lajeunie E, Ma HW, Bonaventure J, Munnich A, Le Merrer M, Renier D.

Nat Genet. 1995 Feb;9(2):108. No abstract available.

PubMed [citation]

PMID:: 7719333

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000034475.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

Description

In a patient with Pfeiffer syndrome (101600) who had Apert syndrome (101200)-like syndactyly, Nagase et al. (1998) detected heterozygosity for an asp321-to-ala (D321A) amino acid substitution in FGFR2. The mutation occurs in the alternatively spliced beta-C-prime-beta-E loop of FGFR2c.

Heterozygosity for the D321A mutation had been described by Lajeunie et al. (1995) in a patient with Pfeiffer syndrome. The substitution resulted from a 974A-C transversion in the FGFR2 gene and was not found in 80 normal controls.

Ibrahimi et al. (2004) demonstrated that the D321A mutation increased the binding affinity of FGFR2c to multiple FGFs expressed in the cranial suture. Additionally, it violated FGFR2c ligand binding specificity and enabled this receptor to bind FGF10.

#	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, SCV000328383.2

#	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

Last Updated: Sep 29, 2024

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