NM_144997.7(FLCN):c.296del (p.Asp99fs) AND Multiple fibrofolliculomas

Clinical significance:Pathogenic (Last evaluated: Aug 19, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000239648.4

Allele description [Variation Report for NM_144997.7(FLCN):c.296del (p.Asp99fs)]

NM_144997.7(FLCN):c.296del (p.Asp99fs)

Gene:
FLCN:folliculin [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
17p11.2
Genomic location:
Preferred name:
NM_144997.7(FLCN):c.296del (p.Asp99fs)
HGVS:
  • NC_000017.11:g.17226276del
  • NG_008001.2:g.15913del
  • NM_001353229.2:c.296del
  • NM_001353230.2:c.296del
  • NM_001353231.2:c.296del
  • NM_144606.7:c.296del
  • NM_144997.7:c.296delMANE SELECT
  • NP_001340158.1:p.Asp99fs
  • NP_001340159.1:p.Asp99fs
  • NP_001340160.1:p.Asp99fs
  • NP_653207.1:p.Asp99fs
  • NP_659434.2:p.Asp99fs
  • LRG_325t1:c.296del
  • LRG_325:g.15913del
  • NC_000017.10:g.17129590del
  • NM_144606.5:c.296delA
  • NM_144997.5:c.296del
  • NM_144997.5:c.296delA
  • p.[Asp99Valfs*31]
Protein change:
D99fs
Links:
dbSNP: rs398124534
NCBI 1000 Genomes Browser:
rs398124534
Molecular consequence:
  • NM_001353229.2:c.296del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001353230.2:c.296del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001353231.2:c.296del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_144606.7:c.296del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_144997.7:c.296del - frameshift variant - [Sequence Ontology: SO:0001589]
Observations:
1

Condition(s)

Name:
Multiple fibrofolliculomas (BHD)
Synonyms:
BHD syndrome; Fibrofolliculomas with trichodiscomas and acrochordons; Hornstein-Knickenberg syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007607; MedGen: C0346010; Orphanet: 122; OMIM: 135150

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000298042Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphiacriteria provided, single submitter
    Pathogenic
    (Jul 18, 2016)
    germlineclinical testing

    DGD_Variant_Analysis_Guidelines.docx,

    SCV000606962GenomeConnect, ClinGenno assertion providednot providedunknownphenotyping only

    SCV000940601Invitaecriteria provided, single submitter
    Pathogenic
    (Aug 19, 2020)
    germlineclinical testing

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

    Description

    Clinical Testing

    SCV000298042

    Summary from all submissions

    EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
    not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
    not providedgermlineyes1not providednot providednot providednot providedclinical testing
    not providedunknownunknownnot providednot providednot providednot providednot providedphenotyping only

    Citations

    PubMed

    BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dubé syndrome: a new series of 50 families and a review of published reports.

    Toro JR, Wei MH, Glenn GM, Weinreich M, Toure O, Vocke C, Turner M, Choyke P, Merino MJ, Pinto PA, Steinberg SM, Schmidt LS, Linehan WM.

    J Med Genet. 2008 Jun;45(6):321-31. doi: 10.1136/jmg.2007.054304. Epub 2008 Jan 30. Review.

    PubMed [citation]
    PMID:
    18234728
    PMCID:
    PMC2564862

    Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubé syndrome.

    Schmidt LS, Nickerson ML, Warren MB, Glenn GM, Toro JR, Merino MJ, Turner ML, Choyke PL, Sharma N, Peterson J, Morrison P, Maher ER, Walther MM, Zbar B, Linehan WM.

    Am J Hum Genet. 2005 Jun;76(6):1023-33. Epub 2005 Apr 25.

    PubMed [citation]
    PMID:
    15852235
    PMCID:
    PMC1196440
    See all PubMed Citations (3)

    Details of each submission

    From Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia, SCV000298042.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not provided1not providednot providedclinical testingnot provided
    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlineyesnot providednot providednot provided1not providednot providednot provided

    From GenomeConnect, ClinGen, SCV000606962.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedphenotyping onlynot provided

    Description

    GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1unknownunknownnot providednot providedvalidationnot providednot providednot providednot provided

    From Invitae, SCV000940601.3

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedclinical testing PubMed (3)

    Description

    This sequence change creates a premature translational stop signal (p.Asp99Valfs*31) in the FLCN gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Birt-Hogg-Dubé syndrome (PMID: 15852235, 18234728). This variant is also known as c.751delA in the literature. ClinVar contains an entry for this variant (Variation ID: 96482). Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235). For these reasons, this variant has been classified as Pathogenic.

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

    Last Updated: Oct 6, 2021

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