NM_000141.5(FGFR2):c.755C>T (p.Ser252Leu) AND FGFR2-related disorder

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 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:: RCV004527721.1

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:: FGFR2-related disorder
Identifiers:

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004105740	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 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

SCV004105740

PreventionGenetics, part of Exact Sciences

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004105740.1

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

Description

The FGFR2 c.755C>T variant is predicted to result in the amino acid substitution p.Ser252Leu. This variant has been reported in several individuals with Crouzon syndrome, but it has also been observed in clinically normal members with the families (Oldridge et al 1997. PubMed ID: 9002682; Sakai N et al 2001. PubMed ID: 11711827; Ohishi et al. 2016. PbuMed ID: 27683237). In one study, functional analysis of this variant revealed wild-type kinetic (Anderson J et al 1998. PubMed ID: 9700203). This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-123279677-G-A). A different substitution affecting the same amino acid (p.Ser252Trp) has been reported in association with Apert syndrome (Human Gene Mutation Database; http://www.hgmd.cf.ac.uk/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

#	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: Nov 10, 2024

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