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NM_000141.5(FGFR2):c.1083A>T (p.Pro361=) AND FGFR2-related craniosynostosis

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 3, 2023
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:
RCV003588493.2

Allele description [Variation Report for NM_000141.5(FGFR2):c.1083A>T (p.Pro361=)]

NM_000141.5(FGFR2):c.1083A>T (p.Pro361=)

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.1083A>T (p.Pro361=)
HGVS:
  • NC_000010.11:g.121517320T>A
  • NG_012449.2:g.86139A>T
  • NM_000141.5:c.1083A>TMANE SELECT
  • NM_001144913.1:c.1087+1362A>T
  • NM_001144914.1:c.749-2001A>T
  • NM_001144915.2:c.816A>T
  • NM_001144916.2:c.738A>T
  • NM_001144917.2:c.939+2659A>T
  • NM_001144918.2:c.738A>T
  • NM_001144919.2:c.820+1362A>T
  • NM_001320654.2:c.399A>T
  • NM_001320658.2:c.1083A>T
  • NM_022970.4:c.1087+1362A>T
  • NM_023029.2:c.816A>T
  • NP_000132.3:p.Pro361=
  • NP_000132.3:p.Pro361=
  • NP_001138387.1:p.Pro272=
  • NP_001138388.1:p.Pro246=
  • NP_001138390.1:p.Pro246=
  • NP_001307583.1:p.Pro133=
  • NP_001307587.1:p.Pro361=
  • NP_075418.1:p.Pro272=
  • LRG_994t1:c.1083A>T
  • LRG_994:g.86139A>T
  • LRG_994p1:p.Pro361=
  • NC_000010.10:g.123276834T>A
  • NM_000141.4:c.1083A>T
  • NR_073009.2:n.1519A>T
Molecular consequence:
  • NM_001144913.1:c.1087+1362A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001144914.1:c.749-2001A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001144917.2:c.939+2659A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001144919.2:c.820+1362A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_022970.4:c.1087+1362A>T - intron variant - [Sequence Ontology: SO:0001627]
  • NR_073009.2:n.1519A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000141.5:c.1083A>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001144915.2:c.816A>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001144916.2:c.738A>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001144918.2:c.738A>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001320654.2:c.399A>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001320658.2:c.1083A>T - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_023029.2:c.816A>T - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Name:
FGFR2-related craniosynostosis
Identifiers:
MedGen: CN231480

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004295735Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 3, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Apparently synonymous substitutions in FGFR2 affect splicing and result in mild Crouzon syndrome.

Fenwick AL, Goos JA, Rankin J, Lord H, Lester T, Hoogeboom AJ, van den Ouweland AM, Wall SA, Mathijssen IM, Wilkie AO.

BMC Med Genet. 2014 Aug 31;15:95. doi: 10.1186/s12881-014-0095-4.

PubMed [citation]
PMID:
25174698
PMCID:
PMC4236556

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004295735.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that this variant is associated with altered splicing resulting in multiple RNA products (PMID: 25174698). This variant has been observed in individual(s) with Crouzon syndrome (PMID: 25174698). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 361 of the FGFR2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the FGFR2 protein. It affects a nucleotide within the consensus splice site.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024