NM_144997.7(FLCN):c.296del (p.Asp99fs) AND Hereditary cancer-predisposing syndrome

Clinical significance:Pathogenic (Last evaluated: Mar 22, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000492350.2

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:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MedGen: C0027672

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000580757Ambry Geneticscriteria provided, single submitter
Pathogenic
(Mar 22, 2018)
germlineclinical testing

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not 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

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

Details of each submission

From Ambry Genetics, SCV000580757.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The c.296delA pathogenic mutation, located in coding exon 2 of the FLCN gene, results from a deletion of one nucleotide at nucleotide position 296, causing a translational frameshift with a predicted alternate stop codon (p.D99Vfs*31). This alteration was previously described in two unrelated families with Birt-Hogg-Dube syndrome, one of which had two family members with fibrofolliculomas and lung cysts, and one of which consisted of an individual with fibrofolliculomas, renal tumors, lung cysts, and multiple pneumothoraces (Toro JR, J. Med. Genet. 2008 Jun; 45(6):321-31; Schmidt LS, Am. J. Hum. Genet. 2005 Jun; 76(6):1023-33). Of note, this alteration is also designated as c.751delA in the published literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Oct 6, 2021

Support Center