Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000198724 | SCV000253766 | pathogenic | Fanconi anemia | 2023-06-23 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Asn164Serfs*3) in the FANCC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FANCC are known to be pathogenic (PMID: 17924555). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. ClinVar contains an entry for this variant (Variation ID: 216037). For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV000984173 | SCV001163627 | pathogenic | Fanconi anemia complementation group C | criteria provided, single submitter | clinical testing | ||
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000984173 | SCV001821465 | likely pathogenic | Fanconi anemia complementation group C | 2021-08-08 | criteria provided, single submitter | clinical testing | Variant summary: FANCC c.489_490delGA (p.Asn164SerfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the 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. The variant allele was found at a frequency of 4e-06 in 251214 control chromosomes. To our knowledge, no occurrence of c.489_490delGA in individuals affected with Fanconi Anemia Group C and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Ambry Genetics | RCV002336539 | SCV002635699 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-03-30 | criteria provided, single submitter | clinical testing | The c.489_490delGA pathogenic mutation, located in coding exon 5 of the FANCC gene, results from a deletion of two nucleotides at nucleotide positions 489 to 490, causing a translational frameshift with a predicted alternate stop codon (p.N164Sfs*3). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Fulgent Genetics, |
RCV000984173 | SCV002806818 | likely pathogenic | Fanconi anemia complementation group C | 2022-05-10 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000984173 | SCV001132188 | likely pathogenic | Fanconi anemia complementation group C | 2015-10-15 | no assertion criteria provided | clinical testing | |
| Leiden Open Variation Database | RCV000984173 | SCV001365298 | pathogenic | Fanconi anemia complementation group C | 2020-02-28 | no assertion criteria provided | curation | Curator: Arleen D. Auerbach. Submitter to LOVD: Arleen D. Auerbach. |