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NM_144997.7(FLCN):c.1063-2A>G AND Hereditary cancer-predisposing syndrome

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 15, 2021
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:
RCV002407057.3

Allele description [Variation Report for NM_144997.7(FLCN):c.1063-2A>G]

NM_144997.7(FLCN):c.1063-2A>G

Gene:
FLCN:folliculin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17p11.2
Genomic location:
Preferred name:
NM_144997.7(FLCN):c.1063-2A>G
HGVS:
  • NC_000017.11:g.17217184T>C
  • NG_008001.2:g.25005A>G
  • NM_001353229.2:c.1117-2A>G
  • NM_001353230.2:c.1063-2A>G
  • NM_001353231.2:c.1063-2A>G
  • NM_144997.7:c.1063-2A>GMANE SELECT
  • LRG_325t1:c.1063-2A>G
  • LRG_325:g.25005A>G
  • NC_000017.10:g.17120498T>C
  • NM_144997.5:c.1063-2A>G
Links:
dbSNP: rs2144871276
NCBI 1000 Genomes Browser:
rs2144871276
Molecular consequence:
  • NM_001353229.2:c.1117-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001353230.2:c.1063-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_001353231.2:c.1063-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
  • NM_144997.7:c.1063-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002716259Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Jun 15, 2021) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Clinical and genetic spectrum of Birt-Hogg-Dube syndrome patients in whom pneumothorax and/or multiple lung cysts are the presenting feature.

Kunogi M, Kurihara M, Ikegami TS, Kobayashi T, Shindo N, Kumasaka T, Gunji Y, Kikkawa M, Iwakami S, Hino O, Takahashi K, Seyama K.

J Med Genet. 2010 Apr;47(4):281-7. doi: 10.1136/jmg.2009.070565.

PubMed [citation]
PMID:
20413710
PMCID:
PMC2981024

Renal cell tumour characteristics in patients with the Birt-Hogg-Dubé cancer susceptibility syndrome: a retrospective, multicentre study.

Benusiglio PR, Giraud S, Deveaux S, Méjean A, Correas JM, Joly D, Timsit MO, Ferlicot S, Verkarre V, Abadie C, Chauveau D, Leroux D, Avril MF, Cordier JF, Richard S; French National Cancer Institute Inherited Predisposition to Kidney Cancer Network..

Orphanet J Rare Dis. 2014 Oct 29;9:163. doi: 10.1186/s13023-014-0163-z.

PubMed [citation]
PMID:
25519458
PMCID:
PMC4219093

Details of each submission

From Ambry Genetics, SCV002716259.2

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

Description

The c.1063-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 7 in the FLCN gene. This variant has been detected in an individual with multiple features of Birt-Hogg-Dube syndrome (BHDS), including fibrofolliculomas, lung cysts and chromophobe renal cell carcinoma (Benusiglio PR et al. Orphanet J Rare Dis, 2014 Oct;9:163). This variant was also detected in a patient with a history of multiple bilateral pneumothoraces (Kunogi M et al. J Med Genet, 2010 Apr;47:281-7). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.

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

Last Updated: Sep 29, 2024