NM_144997.7(FLCN):c.1232_1233dup (p.Ala412fs) AND Birt-Hogg-Dube syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 15, 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:: RCV002816252.3

Allele description [Variation Report for NM_144997.7(FLCN):c.1232_1233dup (p.Ala412fs)]

NM_144997.7(FLCN):c.1232_1233dup (p.Ala412fs)

Gene:

FLCN:folliculin [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_144997.7(FLCN):c.1232_1233dup (p.Ala412fs)

Other names:

p.Ala412Argfs*57

HGVS:

NC_000017.11:g.17216448_17216449dup
NG_008001.2:g.25741_25742dup
NM_001353229.2:c.1286_1287dup
NM_001353230.2:c.1232_1233dup
NM_001353231.2:c.1232_1233dup
NM_144997.7:c.1232_1233dupMANE SELECT
NP_001340158.1:p.Ala430fs
NP_001340159.1:p.Ala412fs
NP_001340160.1:p.Ala412fs
NP_659434.2:p.Ala412Argfs
NP_659434.2:p.Ala412fs
LRG_325t1:c.1231_1232dup
LRG_325:g.25741_25742dup
LRG_325p1:p.Ala412Argfs
NC_000017.10:g.17119760_17119761insCT
NC_000017.10:g.17119762_17119763dup
NM_144997.5:c.1231_1232dup

Protein change:

A412fs

Molecular consequence:

NM_001353229.2:c.1286_1287dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353230.2:c.1232_1233dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001353231.2:c.1232_1233dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_144997.7:c.1232_1233dup - 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
SCV003207236	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 15, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15852235, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003207236

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 15, 2022)

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

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

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, SCV003207236.2

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

Description

This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with FLCN-related conditions. This sequence change creates a premature translational stop signal (p.Ala412Argfs*57) 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

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