NM_000136.3(FANCC):c.1377_1378del (p.Ser459fs) AND Hereditary cancer-predisposing syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 27, 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:: RCV004037669.1

Allele description [Variation Report for NM_000136.3(FANCC):c.1377_1378del (p.Ser459fs)]

NM_000136.3(FANCC):c.1377_1378del (p.Ser459fs)

Genes:

FANCC:FA complementation group C [Gene - OMIM - HGNC]
AOPEP:aminopeptidase O (putative) [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_000136.3(FANCC):c.1377_1378del (p.Ser459fs)

HGVS:

NC_000009.12:g.95107221_95107222del
NG_011707.1:g.215488_215489del
NM_000136.2:c.1377_1378del
NM_000136.3:c.1377_1378delMANE SELECT
NM_001243743.2:c.1377_1378del
NP_000127.2:p.Ser459fs
NP_001230672.1:p.Ser459fs
LRG_497t1:c.1377_1378del
LRG_497:g.215488_215489del
NC_000009.11:g.97869503_97869504del
NM_000136.2:c.1377_1378delCA
NM_000136.3:c.1377_1378del

Protein change:

S459fs

Links:

dbSNP: rs2134456127

NCBI 1000 Genomes Browser:

rs2134456127

Molecular consequence:

NM_000136.3:c.1377_1378del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001243743.2:c.1377_1378del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV005032348	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 27, 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

SCV005032348

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 27, 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

Germline Mutations in Cancer Predisposition Genes are Frequent in Sporadic Sarcomas.

Chan SH, Lim WK, Ishak NDB, Li ST, Goh WL, Tan GS, Lim KH, Teo M, Young CNC, Malik S, Tan MH, Teh JYH, Chin FKC, Kesavan S, Selvarajan S, Tan P, Teh BT, Soo KC, Farid M, Quek R, Ngeow J.

Sci Rep. 2017 Sep 6;7(1):10660. doi: 10.1038/s41598-017-10333-x.

PubMed [citation]

PMID:: 28878254
PMCID:: PMC5587568

Details of each submission

From Ambry Genetics, SCV005032348.1

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

Description

The c.1377_1378delCA pathogenic mutation, located in coding exon 13 of the FANCC gene, results from a deletion of two nucleotides at nucleotide positions 1377 to 1378, causing a translational frameshift with a predicted alternate stop codon (p.S459Rfs*58). This alteration occurs at the 3' terminus of theFANCC gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 100 amino acids of the protein. However, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected (Ambry internal data). This alteration has been identified in an individual diagnosed with a sarcoma (Chan SH et al. Sci Rep, 2017 Sep;7:10660). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, 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: Sep 29, 2024

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