NM_023110.3(FGFR1):c.1966A>G (p.Lys656Glu) AND Encephalocraniocutaneous lipomatosis

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: May 25, 2017)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000210479.3

Allele description [Variation Report for NM_023110.3(FGFR1):c.1966A>G (p.Lys656Glu)]

NM_023110.3(FGFR1):c.1966A>G (p.Lys656Glu)

Gene:
FGFR1:fibroblast growth factor receptor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8p11.23
Genomic location:
Preferred name:
NM_023110.3(FGFR1):c.1966A>G (p.Lys656Glu)
HGVS:
  • NC_000008.11:g.38414790T>C
  • NG_007729.1:g.59045A>G
  • NM_001174063.2:c.1960A>G
  • NM_001174064.2:c.1936A>G
  • NM_001174065.2:c.1960A>G
  • NM_001174066.2:c.1699A>G
  • NM_001174067.2:c.2059A>G
  • NM_001354367.2:c.1960A>G
  • NM_001354368.2:c.1687A>G
  • NM_001354369.2:c.1954A>G
  • NM_001354370.2:c.1693A>G
  • NM_015850.4:c.1960A>G
  • NM_023105.3:c.1699A>G
  • NM_023106.3:c.1693A>G
  • NM_023110.2:c.1966A>G
  • NM_023110.3:c.1966A>GMANE SELECT
  • NP_001167534.1:p.Lys654Glu
  • NP_001167535.1:p.Lys646Glu
  • NP_001167536.1:p.Lys654Glu
  • NP_001167537.1:p.Lys567Glu
  • NP_001167538.1:p.Lys687Glu
  • NP_001341296.1:p.Lys654Glu
  • NP_001341297.1:p.Lys563Glu
  • NP_001341298.1:p.Lys652Glu
  • NP_001341299.1:p.Lys565Glu
  • NP_056934.2:p.Lys654Glu
  • NP_075593.1:p.Lys567Glu
  • NP_075594.1:p.Lys565Glu
  • NP_075598.2:p.Lys656Glu
  • NP_075598.2:p.Lys656Glu
  • LRG_993t1:c.1966A>G
  • LRG_993:g.59045A>G
  • LRG_993p1:p.Lys656Glu
  • NC_000008.10:g.38272308T>C
  • P11362:p.Lys656Glu
Protein change:
K563E; LYS656GLU
Links:
UniProtKB: P11362#VAR_075855; OMIM: 136350.0034; dbSNP: rs869320694
NCBI 1000 Genomes Browser:
rs869320694
Molecular consequence:
  • NM_001174063.2:c.1960A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001174064.2:c.1936A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001174065.2:c.1960A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001174066.2:c.1699A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001174067.2:c.2059A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354367.2:c.1960A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354368.2:c.1687A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354369.2:c.1954A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354370.2:c.1693A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015850.4:c.1960A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_023105.3:c.1699A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_023106.3:c.1693A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_023110.2:c.1966A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_023110.3:c.1966A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Encephalocraniocutaneous lipomatosis (ECCL)
Identifiers:
MONDO: MONDO:0013074; MedGen: C0406612; Orphanet: 2396; OMIM: 613001

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000266575OMIMno assertion criteria providedPathogenic
(Aug 11, 2016)
unknownliterature only

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

SCV000882923University of Washington Center for Mendelian Genomics, University of Washingtonno assertion criteria providedLikely pathogenic
(May 25, 2017)
unknownresearch

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownnot providednot providednot providednot providednot providednot providedliterature only
not providedunknownyesnot providednot providednot providednot providednot providedresearch

Citations

PubMed

Grade II pilocytic astrocytoma in a 3-month-old patient with encephalocraniocutaneous lipomatosis (ECCL): case report and literature review of low grade gliomas in ECCL.

Bieser S, Reis M, Guzman M, Gauvain K, Elbabaa S, Braddock SR, Abdel-Baki MS.

Am J Med Genet A. 2015 Apr;167A(4):878-81. doi: 10.1002/ajmg.a.37017. Epub 2015 Feb 23. Review.

PubMed [citation]
PMID:
25705862

Mosaic Activating Mutations in FGFR1 Cause Encephalocraniocutaneous Lipomatosis.

Bennett JT, Tan TY, Alcantara D, T├ętrault M, Timms AE, Jensen D, Collins S, Nowaczyk MJM, Lindhurst MJ, Christensen KM, Braddock SR, Brandling-Bennett H, Hennekam RCM, Chung B, Lehman A, Su J, Ng S, Amor DJ; University of Washington Center for Mendelian Genomics.; Care4Rare Canada Consortium., Majewski J, Biesecker LG, et al.

Am J Hum Genet. 2016 Mar 3;98(3):579-587. doi: 10.1016/j.ajhg.2016.02.006.

PubMed [citation]
PMID:
26942290
PMCID:
PMC4800051

Details of each submission

From OMIM, SCV000266575.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In a 7-year-old boy (LR12-068) with encephalocraniocutaneous lipomatosis (ECCL; 613001) and an unrelated 2.75-year-old boy (NIH-183) with ECCL who was previously reported by Bieser et al. (2015), Bennett et al. (2016) identified mosaicism for a c.1966A-G transition (c.1966A-G, NM_023110.2) in the FGFR1 gene, resulting in a lys656-to-glu (K656E) substitution within the second tyrosine kinase domain of the cytoplasmic kinase core. In the younger boy, the K656E substitution was present in cultured fibroblasts from affected scalp at an alternate allele fraction (AAF) of 45%, but was not detected in blood. In the older boy, K565E was identified in cultured fibroblasts from a scalp nevus (47% AAF) and in fibroblasts from a pilocytic astrocytoma (32% AAF). The K565E variant was not found in the Exome Variant Server, ExAC, or dbSNP databases. Bennett et al. (2016) stated that K656 is 1 of the 2 residues most commonly mutated among FGFR1 mutation-containing tumors in the Catalogue of Somatic Mutations in Cancer (COSMIC) database, and noted that most of the tumors associated with substitutions in these 2 residues are central nervous system gliomas, including pilocytic astrocytomas, the same type of tumor seen at increased frequency in patients with ECCL. Both boys with the K656E mutation were diagnosed with pilocytic astrocytoma.

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

From University of Washington Center for Mendelian Genomics, University of Washington, SCV000882923.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedresearch PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 20, 2021

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