Submissions for variant NM_000136.3(FANCC):c.246A>G (p.Ala82=)

dbSNP: rs1554857810

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000543469	SCV000626243	uncertain significance	Fanconi anemia	2021-06-17	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FANCC-related disease. This sequence change affects codon 82 of the FANCC mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the FANCC protein. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this is a novel silent change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV004023747	SCV005032383	likely benign	Hereditary cancer-predisposing syndrome	2024-02-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.