ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.17T>A (p.Phe6Tyr) (rs771332058)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000579603 SCV000686329 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-15 criteria provided, single submitter clinical testing
GeneDx RCV000486672 SCV000566537 uncertain significance not provided 2015-05-11 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.17T>A at the cDNA level, p.Phe6Tyr (F6Y) at the protein level, and results in the change of a Phenylalanine to a Tyrosine (TTC>TAC). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51C Phe6Tyr was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Phenylalanine and Tyrosine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. RAD51C Phe6Tyr occurs at a position that is not conserved and is located in the region required for Holliday junction resolution activity (UniProt). In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available information, it is unclear whether RAD51C Phe6Tyr is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000465983 SCV000550207 uncertain significance Fanconi anemia, complementation group O 2018-05-18 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with tyrosine at codon 6 of the RAD51C protein (p.Phe6Tyr). The phenylalanine residue is weakly conserved and there is a small physicochemical difference between phenylalanine and tyrosine. This variant is present in population databases (rs771332058, ExAC 0.002%). This variant has not been reported in the literature in individuals with RAD51C-related disease. ClinVar contains an entry for this variant (Variation ID: 409849). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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