Submissions for variant NM_058216.3(RAD51C):c.234A>G (p.Thr78=)

gnomAD frequency: 0.00001  dbSNP: rs730881929

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000212937	SCV000211625	uncertain significance	not provided	2018-12-05	criteria provided, single submitter	clinical testing	This variant is denoted RAD51C c.234A>G at the DNA level. It is silent at the coding level, preserving a Threonine at codon 78. In silico analyses, which include splice predictors and evolutionary conservation, are inconsistent in their assessment as to whether or not the variant is damaging. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51C c.234A>G was not observed at a significant allele frequency in large population cohorts (Lek 2016). Based on currently available information, it is unclear whether RAD51C c.234A>G is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics	RCV000160921	SCV000213693	likely benign	Hereditary cancer-predisposing syndrome	2014-12-15	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Invitae	RCV000477301	SCV000550200	uncertain significance	Fanconi anemia complementation group O	2024-01-16	criteria provided, single submitter	clinical testing	This sequence change affects codon 78 of the RAD51C mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RAD51C protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is present in population databases (rs730881929, gnomAD 0.006%). This variant has been observed in individual(s) with biliary tract cancer (PMID: 36243179). ClinVar contains an entry for this variant (Variation ID: 182833). Studies have shown that this variant results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. 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.
Counsyl	RCV000663292	SCV000786534	likely benign	Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O	2018-05-18	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000160921	SCV001342998	likely benign	Hereditary cancer-predisposing syndrome	2018-12-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001192878	SCV001361303	likely benign	not specified	2019-11-28	criteria provided, single submitter	clinical testing