NM_144997.7(FLCN):c.927dup (p.Ala310fs) AND Multiple fibrofolliculomas

Clinical significance:Pathogenic (Last evaluated: Jan 26, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000239698.3

Allele description [Variation Report for NM_144997.7(FLCN):c.927dup (p.Ala310fs)]

NM_144997.7(FLCN):c.927dup (p.Ala310fs)

Gene:
FLCN:folliculin [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
17p11.2
Genomic location:
Preferred name:
NM_144997.7(FLCN):c.927dup (p.Ala310fs)
HGVS:
  • NC_000017.11:g.17219156dup
  • NG_008001.2:g.23035dup
  • NM_001353229.2:c.981dup
  • NM_001353230.2:c.927dup
  • NM_001353231.2:c.927dup
  • NM_144997.7:c.927dupMANE SELECT
  • NP_001340158.1:p.Ala328fs
  • NP_001340159.1:p.Ala310fs
  • NP_001340160.1:p.Ala310fs
  • NP_659434.2:p.Ala310fs
  • LRG_325t1:c.927dup
  • LRG_325:g.23035dup
  • NC_000017.10:g.17122467_17122468insT
  • NC_000017.10:g.17122470dup
  • NM_144997.5:c.927dup
  • NM_144997.5:c.927dupA
  • p.[Ala310Serfs*80]
Protein change:
A310fs
Links:
dbSNP: rs879255669
NCBI 1000 Genomes Browser:
rs879255669
Molecular consequence:
  • NM_001353229.2:c.981dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001353230.2:c.927dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001353231.2:c.927dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_144997.7:c.927dup - 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
SCV000298066Genomic 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,

    SCV001203985Invitaecriteria provided, single submitter
    Pathogenic
    (Jan 26, 2020)
    germlineclinical testing

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

    Description

    Clinical Testing

    SCV000298066

    Summary from all submissions

    EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
    not providedgermlineunknown1not providednot providednot providednot providedclinical testing

    Citations

    PubMed

    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

    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):240-242.

    PubMed [citation]
    PMID:
    28492532
    PMCID:
    PMC5632818

    Details of each submission

    From Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia, SCV000298066.1

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

    From Invitae, SCV001203985.2

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

    Description

    This sequence change creates a premature translational stop signal (p.Ala310Serfs*80) 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 not been reported in the literature in individuals with FLCN-related conditions. ClinVar contains an entry for this variant (Variation ID: 253241). 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: Nov 27, 2021

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