Submissions for variant NM_000136.3(FANCC):c.489_490del (p.Asn164fs)

dbSNP: rs730881708

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000198724	SCV000253766	pathogenic	Fanconi anemia	2023-06-23	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 216037). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). 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).
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, LabCorp	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, Fulgent Genetics	RCV000984173	SCV002806818	likely pathogenic	Fanconi anemia complementation group C	2024-03-12	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.