NM_144997.7(FLCN):c.250-2A>G AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jul 8, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000082633.19

Allele description [Variation Report for NM_144997.7(FLCN):c.250-2A>G]

NM_144997.7(FLCN):c.250-2A>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.250-2A>G

HGVS:

NC_000017.11:g.17226324T>C
NG_008001.2:g.15865A>G
NM_001353229.2:c.250-2A>G
NM_001353230.2:c.250-2A>G
NM_001353231.2:c.250-2A>G
NM_144606.7:c.250-2A>G
NM_144997.7:c.250-2A>GMANE SELECT
LRG_325t1:c.250-2A>G
LRG_325:g.15865A>G
NC_000017.10:g.17129638T>C
NM_144997.5:c.250-2A>G
NM_144997.6:c.250-2A>G

Nucleotide change:

IVS4AS, A-G, -2

Links:

OMIM: 607273.0014; dbSNP: rs398124533

NCBI 1000 Genomes Browser:

rs398124533

Molecular consequence:

NM_001353229.2:c.250-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001353230.2:c.250-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001353231.2:c.250-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_144606.7:c.250-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_144997.7:c.250-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000114675	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Aug 2, 2012)	germline	clinical testing	Citation Link,
SCV000321650	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jan 31, 2023)	germline	clinical testing	Citation Link,
SCV004219715	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jul 8, 2023)	unknown	clinical testing	PubMed (7) [See all records that cite these PMIDs] 31958439, 25610687, 19562744, 18234728, 35639097, 34654685, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000114675

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Aug 2, 2012)

germline

clinical testing

Citation Link,

SCV000321650

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jan 31, 2023)

germline

clinical testing

Citation Link,

SCV004219715

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Pathogenic
(Jul 8, 2023)

unknown

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	3	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic Risk Factors for Spontaneous Pneumothorax in Birt-Hogg-Dubé Syndrome.

Sattler EC, Syunyaeva Z, Mansmann U, Steinlein OK.

Chest. 2020 May;157(5):1199-1206. doi: 10.1016/j.chest.2019.12.019. Epub 2020 Jan 17.

PubMed [citation]

PMID:: 31958439

A rare soft tissue tumor masquerading as a parathyroid adenoma in a patient with birt-hogg-dubé syndrome and multiple cervical endocrinopathies.

Mikesell KV, Kulaylat AN, Donaldson KJ, Saunders BD, Crist HS.

Case Rep Pathol. 2014;2014:753694. doi: 10.1155/2014/753694. Epub 2014 Dec 25.

PubMed [citation]

PMID:: 25610687
PMCID:: PMC4290639

See all PubMed Citations (7)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000114675.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		3	not provided	not provided	not provided

From GeneDx, SCV000321650.12

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown; Deletions involving coding exons of this gene are a known mechanism of disease (HGMD); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19802896, 29357828, 18234728, 25610687, 21937013, 25525159, 31958439, 34654685)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004219715.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

The FLCN c.250-2A>G variant disrupts a canonical splice-acceptor site and interferes with normal FLCN mRNA splicing. This variant has been reported in the published literature in several affected individuals and families with Birt-Hogg-Dubé syndrome (PMIDs: 18234728 (2008), 31958439 (2020), and 35639097 (2022)). It has also been reported in early onset renal cell carcinoma (PMID: 34654685 (2021)) and rhabdomyoma (PMID: 25610687 (2014)). Based on the available information, this variant is classified as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 5, 2025

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