ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.29G>A (p.Cys10Tyr) (rs143152201)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000656849 SCV000149257 uncertain significance not provided 2018-08-27 criteria provided, single submitter clinical testing This variant is denoted FANCC c.29G>A at the cDNA level, p.Cys10Tyr (C10Y) at the protein level, and results in the change of a Cysteine to a Tyrosine (TGT>TAT). This variant has been observed in individuals with breast cancer, pancreatic cancer, low-grade glioma, and acute myeloid leukemia (Lu 2015, Cabanillas 2017). FANCC Cys10Tyr was observed at an allele frequency of 0.15% (46/30,778) in individuals of South Asian ancestry in large population cohorts (Lek 2016). This variant is located in the region of interaction with RED (Gordon 2000). In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether FANCC Cys10Tyr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000233348 SCV000283589 uncertain significance Fanconi anemia 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 10 of the FANCC protein (p.Cys10Tyr). The cysteine residue is weakly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is present in population databases (rs143152201, ExAC 0.2%). This variant has been reported in an individual affected with breast cancer (PMID: 26689913). ClinVar contains an entry for this variant (Variation ID: 127538). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000656849 SCV000345144 uncertain significance not provided 2016-08-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000567825 SCV000673308 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-02 criteria provided, single submitter clinical testing Insufficient evidence
Mendelics RCV000709097 SCV000838362 uncertain significance Fanconi anemia, complementation group C 2018-07-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000709097 SCV001330589 uncertain significance Fanconi anemia, complementation group C 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.