ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.65G>A (p.Trp22Ter) (rs377294947)

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
Counsyl RCV000169293 SCV000220611 likely pathogenic Fanconi anemia, complementation group C 2014-08-20 criteria provided, single submitter literature only
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169293 SCV000695435 pathogenic Fanconi anemia, complementation group C 2017-08-14 criteria provided, single submitter clinical testing Variant summary: The FANCC c.65G>A (p.Trp22X) variant results in a premature termination codon, predicted to cause a truncated or absent FANCC protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g.c.67delG/p.Asp23fsX23, c.1642C>T/p.Arg548X). One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/121148 control chromosomes at a frequency of 0.0000083, which does not exceed the estimated maximal expected allele frequency of a pathogenic FANCC variant (0.0017678). This variant has been reported in at least three patients with Fanconi Anemia. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/likely pathogenic. Taken together, this variant is classified as pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000169293 SCV000894485 pathogenic Fanconi anemia, complementation group C 2018-10-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV000169293 SCV001163260 pathogenic Fanconi anemia, complementation group C criteria provided, single submitter clinical testing
Invitae RCV001390247 SCV001591920 pathogenic Fanconi anemia 2020-09-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp22*) in the FANCC gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs377294947, ExAC 0.01%). This variant has been observed in individual(s) with clinical features of Fanconi anemia (PMID: 8844212, 28717661). ClinVar contains an entry for this variant (Variation ID: 188926). 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. Loss-of-function variants in FANCC are known to be pathogenic (PMID: 17924555). For these reasons, this variant has been classified as Pathogenic.
Leiden Open Variation Database RCV000169293 SCV001365307 pathogenic Fanconi anemia, complementation group C 2020-02-28 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitters to LOVD: Arleen D. Auerbach, Daniela Pilonetto, 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.