NM_000136.3(FANCC):c.1517G>A (p.Trp506Ter) AND Fanconi anemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 30, 2021
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:: RCV001850946.6

Allele description [Variation Report for NM_000136.3(FANCC):c.1517G>A (p.Trp506Ter)]

NM_000136.3(FANCC):c.1517G>A (p.Trp506Ter)

Genes:

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

Variant type:

single nucleotide variant

Cytogenetic location:

9q22.32

Genomic location:

Preferred name:

NM_000136.3(FANCC):c.1517G>A (p.Trp506Ter)

HGVS:

NC_000009.12:g.95107082C>T
NG_011707.1:g.215628G>A
NM_000136.3:c.1517G>AMANE SELECT
NM_001243743.2:c.1517G>A
NP_000127.2:p.Trp506Ter
NP_001230672.1:p.Trp506Ter
LRG_497t1:c.1517G>A
LRG_497:g.215628G>A
NC_000009.11:g.97869364C>T
NM_000136.2:c.1517G>A

Protein change:

W506*

Links:

dbSNP: rs1057516488

NCBI 1000 Genomes Browser:

rs1057516488

Molecular consequence:

NM_000136.3:c.1517G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001243743.2:c.1517G>A - nonsense - [Sequence Ontology: SO:0001587]

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
SCV002242890	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 30, 2021)	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

SCV002242890

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 30, 2021)

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, SCV002242890.3

#	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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 370437). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Trp506*) in the FANCC gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 53 amino acid(s) of the FANCC 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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