Submissions for variant NM_000136.3(FANCC):c.576C>G (p.Thr192=)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002643399	SCV002986360	uncertain significance	Fanconi anemia	2022-03-28	criteria provided, single submitter	clinical testing	This sequence change affects codon 192 of the FANCC mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the FANCC protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FANCC-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV004066757	SCV005032324	likely benign	Hereditary cancer-predisposing syndrome	2024-03-10	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.