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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 23, 2020
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:: RCV001385163.7

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:: Fanconi anemia (FA)
Synonyms:: Fanconi pancytopenia; Fanconi's anemia
Identifiers:: MONDO: MONDO:0019391; MeSH: D005199; MedGen: C0015625; Orphanet: 84; OMIM: PS227650

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001584925	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 23, 2020)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 8103176, 24584348, 8882868, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001584925

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 23, 2020)

germline

clinical testing

PubMed (4)
[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

FACC gene mutations and early prenatal diagnosis of Fanconi's anaemia.

Murer-Orlando M, Llerena JC Jr, Birjandi F, Gibson RA, Mathew CG.

Lancet. 1993 Sep 11;342(8872):686. No abstract available.

PubMed [citation]

PMID:: 8103176

Molecular analysis of Fanconi anemia: the experience of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Onco-Hematology.

De Rocco D, Bottega R, Cappelli E, Cavani S, Criscuolo M, Nicchia E, Corsolini F, Greco C, Borriello A, Svahn J, Pillon M, Mecucci C, Casazza G, Verzegnassi F, Cugno C, Locasciulli A, Farruggia P, Longoni D, Ramenghi U, Barberi W, Tucci F, Perrotta S, et al.

Haematologica. 2014 Jun;99(6):1022-31. doi: 10.3324/haematol.2014.104224. Epub 2014 Feb 28. Erratum in: Haematologica. 2014 Sep;99(9):1532.

PubMed [citation]

PMID:: 24584348
PMCID:: PMC4040906

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001584925.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the FANCC protein. Other variant(s) that disrupt this region (p.Arg548*) have been determined to be pathogenic (PMID: 8103176, 24584348, 8882868). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This sequence change results in a premature translational stop signal in the FANCC gene (p.Ser459Argfs*58). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 100 amino acids of the FANCC protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FANCC-related conditions.

#	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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