ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.844-1G>C (rs774209201)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169449 SCV000220870 likely pathogenic Fanconi anemia, complementation group C 2014-11-12 criteria provided, single submitter literature only
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224795 SCV000281409 pathogenic not provided 2015-09-29 criteria provided, single submitter clinical testing
GeneDx RCV000224795 SCV000517421 pathogenic not provided 2020-06-09 criteria provided, single submitter clinical testing Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek 2016); This variant is associated with the following publications: (PMID: 25525159, 22720145, 17924555, 29922827, 31589614)
Invitae RCV000462508 SCV000549969 likely pathogenic Fanconi anemia 2020-09-30 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 8 of the FANCC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is present in population databases (rs774209201, ExAC 0.002%). This variant has been observed in compound heterozygosity with two different pathogenic FANCC variants in two patients with suspected Fanconi anemia (PMID: 17924555). ClinVar contains an entry for this variant (Variation ID: 189053). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FANCC are known to be pathogenic (PMID: 17924555). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169449 SCV000917334 likely pathogenic Fanconi anemia, complementation group C 2017-12-18 criteria provided, single submitter clinical testing Variant summary: The FANCC c.844-1G>C variant involves the alteration of a conserved intronic nucleotide and 5/5 splice prediction tools predict the variant to abolish a cannonical splice acceptor site. However, these predictions have yet to be confirmed by functional studies. This variant was found in 2/246200 control chromosomes (gnomAD) at a frequency of 0.0000081, which does not exceed the estimated maximal expected allele frequency of a pathogenic FANCC variant (0.0017678). The variant has been reported, to our knowledge, in one publication citing two affected individuals (Ameziane_2008). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as likely pathogenic.
Ambry Genetics RCV001017779 SCV001178923 pathogenic Hereditary cancer-predisposing syndrome 2018-08-08 criteria provided, single submitter clinical testing The c.844-1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide upstream from coding exon 8 of the FANCC gene. This alteration was seen in two patients with Fanconi Anemia who were diagnosed with chromosomal breakage analysis (Ameziane N et al. Hum. Mutat. 2008 Jan;29:159-66). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
Leiden Open Variation Database RCV000169449 SCV001365325 pathogenic Fanconi anemia, complementation group C 2020-02-28 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Johan de Winter.

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.