NM_144997.7(FLCN):c.1584del (p.Glu530fs) AND Birt-Hogg-Dube syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 3, 2023
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:: RCV001851346.6

Allele description [Variation Report for NM_144997.7(FLCN):c.1584del (p.Glu530fs)]

NM_144997.7(FLCN):c.1584del (p.Glu530fs)

Gene:

FLCN:folliculin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_144997.7(FLCN):c.1584del (p.Glu530fs)

HGVS:

NC_000017.11:g.17213813del
NG_008001.2:g.28378del
NM_001353229.2:c.1638del
NM_001353230.2:c.1584del
NM_001353231.2:c.1584del
NM_144997.7:c.1584delMANE SELECT
NP_001340158.1:p.Glu548fs
NP_001340159.1:p.Glu530fs
NP_001340160.1:p.Glu530fs
NP_659434.2:p.Glu530fs
LRG_325t1:c.1584del
LRG_325:g.28378del
NC_000017.10:g.17117125del
NC_000017.10:g.17117127del
NM_144997.5:c.1584delC

Protein change:

E530fs

Links:

dbSNP: rs1131690827

NCBI 1000 Genomes Browser:

rs1131690827

Molecular consequence:

NM_001353229.2:c.1638del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353230.2:c.1584del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353231.2:c.1584del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_144997.7:c.1584del - 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
SCV002110057	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 3, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28558743, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002110057

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 3, 2023)

germline

clinical testing

PubMed (2)
[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

Clinical and genetic characteristics of chinese patients with Birt-Hogg-Dubé syndrome.

Liu Y, Xu Z, Feng R, Zhan Y, Wang J, Li G, Li X, Zhang W, Hu X, Tian X, Xu KF, Zhang X.

Orphanet J Rare Dis. 2017 May 30;12(1):104. doi: 10.1186/s13023-017-0656-7.

PubMed [citation]

PMID:: 28558743
PMCID:: PMC5450333

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002110057.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant disrupts a region of the FLCN protein in which other variant(s) (p.Trp553*) have been determined to be pathogenic (PMID: 28558743). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 428639). This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu530Argfs*7) in the FLCN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 50 amino acid(s) of the FLCN protein.

#	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

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