NM_144997.7(FLCN):c.228del (p.Lys78fs) AND Birt-Hogg-Dube syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 25, 2022
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:: RCV001217352.5

Allele description [Variation Report for NM_144997.7(FLCN):c.228del (p.Lys78fs)]

NM_144997.7(FLCN):c.228del (p.Lys78fs)

Gene:

FLCN:folliculin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_144997.7(FLCN):c.228del (p.Lys78fs)

HGVS:

NC_000017.11:g.17227912del
NG_008001.2:g.14279del
NM_001353229.2:c.228del
NM_001353230.2:c.228del
NM_001353231.2:c.228del
NM_144606.7:c.228del
NM_144997.7:c.228delMANE SELECT
NP_001340158.1:p.Lys78fs
NP_001340159.1:p.Lys78fs
NP_001340160.1:p.Lys78fs
NP_653207.1:p.Lys78fs
NP_659434.2:p.Lys78fs
LRG_325t1:c.228del
LRG_325:g.14279del
NC_000017.10:g.17131224del
NC_000017.10:g.17131226del
NM_144997.5:c.228del

Protein change:

K78fs

Links:

dbSNP: rs2047302808

NCBI 1000 Genomes Browser:

rs2047302808

Molecular consequence:

NM_001353229.2:c.228del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353230.2:c.228del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353231.2:c.228del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_144606.7:c.228del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_144997.7:c.228del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Birt-Hogg-Dube syndrome
Synonyms:: BHD syndrome; Birt Hogg Dubé syndrome
Identifiers:: MONDO: MONDO:0800444; MedGen: C0346010; Orphanet: 122; OMIM: PS135150

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001389188	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 25, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27734835, 15852235, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001389188

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 25, 2022)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic screening of the FLCN gene identify six novel variants and a Danish founder mutation.

Rossing M, Albrechtsen A, Skytte AB, Jensen UB, Ousager LB, Gerdes AM, Nielsen FC, Hansen TV.

J Hum Genet. 2017 Feb;62(2):151-157. doi: 10.1038/jhg.2016.118. Epub 2016 Oct 13.

PubMed [citation]

PMID:: 27734835

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001389188.4

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 946478). This premature translational stop signal has been observed in individual(s) with fibrofolliculomas (PMID: 27734835). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Lys78Serfs*52) in the FLCN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FLCN are known to be pathogenic (PMID: 15852235).

#	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		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

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