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NM_000136.3(FANCC):c.1661T>C (p.Leu554Pro)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
9 (Most recent: Jul 20, 2021)
Last evaluated:
Dec 3, 2020
Accession:
VCV000012043.12
Variation ID:
12043
Description:
single nucleotide variant
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NM_000136.3(FANCC):c.1661T>C (p.Leu554Pro)

Allele ID
27082
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
9q22.32
Genomic location
9: 95101723 (GRCh38) GRCh38 UCSC
9: 97864005 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
Q00597:p.Leu554Pro
NC_000009.11:g.97864005A>G
NC_000009.12:g.95101723A>G
... more HGVS
Protein change
L554P
Other names
-
Canonical SPDI
NC_000009.12:95101722:A:G
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00002
The Genome Aggregation Database (gnomAD) 0.00003
Links
ClinGen: CA284829
UniProtKB: Q00597#VAR_005233
OMIM: 613899.0001
dbSNP: rs104886458
VarSome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 6 criteria provided, multiple submitters, no conflicts Oct 14, 2019 RCV000012823.10
Pathogenic 2 criteria provided, single submitter Dec 3, 2020 RCV000058925.5
Pathogenic 1 criteria provided, single submitter Jul 23, 2020 RCV001221431.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
AOPEP - - GRCh38
GRCh37
6 640
FANCC - - GRCh38
GRCh37
437 1074

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Likely pathogenic
(-)
criteria provided, single submitter
Method: clinical testing
Fanconi anemia, complementation group C
Allele origin: germline
Baylor Genetics
Accession: SCV001163619.1
Submitted: (Sep 27, 2019)
Evidence details
Pathogenic
(Oct 14, 2019)
criteria provided, single submitter
Method: clinical testing
Fanconi anemia, complementation group C
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001363461.1
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (8)
Comment:
Variant summary: FANCC c.1661T>C (p.Leu554Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging … (more)
Pathogenic
(Jul 23, 2020)
criteria provided, single submitter
Method: clinical testing
Fanconi anemia
Allele origin: germline
Invitae
Accession: SCV001393476.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces leucine with proline at codon 554 of the FANCC protein (p.Leu554Pro). The leucine residue is moderately conserved and there is a … (more)
Pathogenic
(Dec 03, 2020)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000512973.5
Submitted: (Jul 20, 2021)
Evidence details
Comment:
Identified in two siblings with Fanconi anemia (Verlander 1994); Identified in individuals with breast and other cancers (Thompson 2012, Chandrasekharappa 2017); Published functional studies demonstrate … (more)
Likely pathogenic
(Oct 09, 2018)
no assertion criteria provided
Method: clinical testing
Fanconi anemia, complementation group C
Allele origin: unknown
Counsyl
Accession: SCV001132190.1
Submitted: (Aug 05, 2019)
Evidence details
Publications
PubMed (8)
Pathogenic
(Jun 01, 2021)
no assertion criteria provided
Method: literature only
Fanconi anemia, complementation group C
Allele origin: germline
GeneReviews
Accession: SCV000057806.3
Submitted: (Jun 08, 2021)
Evidence details
Publications
PubMed (1)
BookShelf: NBK1401
Pathogenic
(Feb 01, 1993)
no assertion criteria provided
Method: literature only
FANCONI ANEMIA, COMPLEMENTATION GROUP C
Allele origin: germline
OMIM
Accession: SCV000033063.3
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (3)
Gavish, H., dos Santos, C. C.,  (more...)
Pathogenic
(Feb 28, 2020)
no assertion criteria provided
Method: curation
Fanconi anemia, complementation group C
Allele origin: germline
Leiden Open Variation Database
Accession: SCV001365344.1
Submitted: (Feb 28, 2020)
Evidence details
Publications
PubMed (1)
Comment:
Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach.
not provided
(-)
no assertion provided
Method: not provided
not provided
Allele origin: germline
SNPedia
Accession: SCV000090446.1
Submitted: (Apr 26, 2011)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
Fanconi Anemia Mehta PA - 2021 PMID: 20301575
The Fanconi Anemia C Protein Binds to and Regulates Stathmin-1 Phosphorylation. Magron A PloS one 2015 PMID: 26466335
The Fanconi anemia pathway has a dual function in Dickkopf-1 transcriptional repression. Huard CC Proceedings of the National Academy of Sciences of the United States of America 2014 PMID: 24469828
Exome sequencing identifies rare deleterious mutations in DNA repair genes FANCC and BLM as potential breast cancer susceptibility alleles. Thompson ER PLoS genetics 2012 PMID: 23028338
Intermediate DNA repair activity associated with the 322delG allele of the fanconi anemia complementation group C gene. Donahue SL Journal of molecular biology 2004 PMID: 15364573
FANCE: the link between Fanconi anaemia complex assembly and activity. Pace P The EMBO journal 2002 PMID: 12093742
The fanconi anemia proteins FANCA and FANCG stabilize each other and promote the nuclear accumulation of the Fanconi anemia complex. Garcia-Higuera I Blood 2000 PMID: 11050007
The Fanconi anaemia proteins, FAA and FAC, interact to form a nuclear complex. Kupfer GM Nature genetics 1997 PMID: 9398857
The Fanconi anemia polypeptide, FAC, binds to the cyclin-dependent kinase, cdc2. Kupfer GM Blood 1997 PMID: 9242535
Phenotypic consequences of mutations in the Fanconi anemia FAC gene: an International Fanconi Anemia Registry study. Gillio AP Blood 1997 PMID: 9207444
Positive diepoxybutane test in only one of two brothers found to be compound heterozygotes for Fanconi's anaemia complementation group C mutations. Dokal I British journal of haematology 1996 PMID: 8703809
Cytoplasmic localization of FAC is essential for the correction of a prerepair defect in Fanconi anemia group C cells. Youssoufian H The Journal of clinical investigation 1996 PMID: 8621788
Induction of Fanconi anemia cellular phenotype in human 293 cells by overexpression of a mutant FAC allele. Youssoufian H The Journal of clinical investigation 1996 PMID: 8613549
Mutation analysis of the Fanconi anemia gene FACC. Verlander PC American journal of human genetics 1994 PMID: 8128956
A Leu554-to-Pro substitution completely abolishes the functional complementing activity of the Fanconi anemia (FACC) protein. Gavish H Human molecular genetics 1993 PMID: 8499901
Cloning of cDNAs for Fanconi's anaemia by functional complementation. Strathdee CA Nature 1992 PMID: 1641028
Cloning of cDNAs for Fanconi's anaemia by functional complementation. Strathdee CA Nature 1992 PMID: 1574115
Gavish, H., dos Santos, C. C., Buchwald, M. Generation of a non-functional Fanconi anemia group C protein (FACC) by site-directed in vitro mutagenesis. (Abstract) Am. J. Hum. Genet. 51 (suppl.): A128-only, 1992. - - - -

Text-mined citations for rs104886458...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 20, 2021