NM_000141.5(FGFR2):c.1274G>A (p.Arg425Gln) AND FGFR2-related craniosynostosis

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 22, 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:: RCV002664133.2

Allele description

NM_000141.5(FGFR2):c.1274G>A (p.Arg425Gln)

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.1274G>A (p.Arg425Gln)

HGVS:

NC_000010.11:g.121515130C>T
NG_012449.2:g.88329G>A
NM_000141.5:c.1274G>AMANE SELECT
NM_001144913.1:c.1277G>A
NM_001144914.1:c.938G>A
NM_001144915.2:c.1007G>A
NM_001144916.2:c.929G>A
NM_001144917.2:c.939+4849G>A
NM_001144918.2:c.929G>A
NM_001144919.2:c.1010G>A
NM_001320654.2:c.590G>A
NM_001320658.2:c.1274G>A
NM_022969.1:c.1277G>A
NM_022970.4:c.1277G>A
NM_023029.2:c.1007G>A
NP_000132.3:p.Arg425Gln
NP_000132.3:p.Arg425Gln
NP_001138385.1:p.Arg426Gln
NP_001138386.1:p.Arg313Gln
NP_001138387.1:p.Arg336Gln
NP_001138388.1:p.Arg310Gln
NP_001138390.1:p.Arg310Gln
NP_001138391.1:p.Arg337Gln
NP_001307583.1:p.Arg197Gln
NP_001307587.1:p.Arg425Gln
NP_075258.1:p.Arg426Gln
NP_075259.4:p.Arg426Gln
NP_075259.4:p.Arg426Gln
NP_075418.1:p.Arg336Gln
LRG_994t1:c.1274G>A
LRG_994t2:c.1277G>A
LRG_994:g.88329G>A
LRG_994p1:p.Arg425Gln
LRG_994p2:p.Arg426Gln
NC_000010.10:g.123274644C>T
NM_000141.4:c.1274G>A
NM_022970.3:c.1277G>A
NR_073009.2:n.1710G>A

Protein change:

R197Q

Molecular consequence:

NM_001144917.2:c.939+4849G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000141.5:c.1274G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001144913.1:c.1277G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001144914.1:c.938G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001144915.2:c.1007G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001144916.2:c.929G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001144918.2:c.929G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001144919.2:c.1010G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001320654.2:c.590G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001320658.2:c.1274G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022969.1:c.1277G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022970.4:c.1277G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_023029.2:c.1007G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_073009.2:n.1710G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: FGFR2-related craniosynostosis
Identifiers:: MedGen: CN231480

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003522523	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 22, 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

SCV003522523

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 22, 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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003522523.2

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with FGFR2-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 425 of the FGFR2 protein (p.Arg425Gln).

#	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: Feb 14, 2024

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