NM_144997.7(FLCN):c.33C>A (p.Cys11Ter) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 6, 2024
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:: RCV000492609.4

Allele description [Variation Report for NM_144997.7(FLCN):c.33C>A (p.Cys11Ter)]

NM_144997.7(FLCN):c.33C>A (p.Cys11Ter)

Gene:

FLCN:folliculin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_144997.7(FLCN):c.33C>A (p.Cys11Ter)

HGVS:

NC_000017.11:g.17228105G>T
NG_008001.2:g.14084C>A
NM_001353229.2:c.33C>A
NM_001353230.2:c.33C>A
NM_001353231.2:c.33C>A
NM_144606.7:c.33C>A
NM_144997.6:c.33C>A
NM_144997.7:c.33C>AMANE SELECT
NP_001340158.1:p.Cys11Ter
NP_001340159.1:p.Cys11Ter
NP_001340160.1:p.Cys11Ter
NP_653207.1:p.Cys11Ter
NP_659434.2:p.Cys11Ter
LRG_325t1:c.33C>A
LRG_325:g.14084C>A
NC_000017.10:g.17131419G>T
NM_144997.5:c.33C>A
NM_144997.7:c.33C>A

Protein change:

C11*

Links:

dbSNP: rs754616167

NCBI 1000 Genomes Browser:

rs754616167

Molecular consequence:

NM_001353229.2:c.33C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353230.2:c.33C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001353231.2:c.33C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_144606.7:c.33C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_144997.7:c.33C>A - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000580732	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Mar 6, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000580732

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Mar 6, 2024)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

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

Frequency of pathogenic germline variants in cancer susceptibility genes in 1336 renal cell carcinoma cases.

Yngvadottir B, Andreou A, Bassaganyas L, Larionov A, Cornish AJ, Chubb D, Saunders CN, Smith PS, Zhang H, Cole Y, Research Consortium GE, Larkin J, Browning L, Turajlic S, Litchfield K, Houlston RS, Maher ER.

Hum Mol Genet. 2022 Aug 25;31(17):3001-3011. doi: 10.1093/hmg/ddac089.

PubMed [citation]

PMID:: 35441217
PMCID:: PMC9433729

Details of each submission

From Ambry Genetics, SCV000580732.6

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

Description

The p.C11* pathogenic mutation (also known as c.33C>A), located in coding exon 1 of the FLCN gene, results from a C to A substitution at nucleotide position 33. This changes the amino acid from a cysteine to a stop codon within coding exon 1. In a series of 1336 individuals with renal cell carcinoma, this alteration was observed once (Yngvadottir B et al. Hum Mol Genet, 2022 Aug;31:3001-3011). This variant has been observed in at least one individual with a personal and/or family history that is consistent with Birt-Hogg-Dube syndrome (Ambry internal data). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). As such, this alteration is interpreted as a disease-causing mutation.

#	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: Oct 8, 2024

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