ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.222A>G (p.Arg74=)

dbSNP: rs2047945471
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001340640 SCV001534462 uncertain significance Fanconi anemia complementation group O 2022-03-09 criteria provided, single submitter clinical testing 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 1037480). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 74 of the RAD51C mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the RAD51C protein.
Color Diagnostics, LLC DBA Color Health RCV001524269 SCV001734067 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This synonymous variant does not change the amino acid sequence of the RAD51C protein. Splice site prediction tools suggest that this variant may create a new splice donor site, although this prediction has not been confirmed in published RNA studies. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001524269 SCV003993247 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-18 criteria provided, single submitter clinical testing The c.222A>G variant (also known as p.R74R), located in coding exon 2 of the RAD51C gene, results from an A to G substitution at nucleotide position 222. This nucleotide substitution does not change the codon at 74. However, this change occurs in the base pair of coding exon 2, which makes it likely to have some effect on normal mRNA splicing. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice donor site. RNA studies have demonstrated that this alteration results in a transcript predicted to lead to a protein with an in-frame deletion of 62 and insertion of 1 amino acid(s); however, the exact functional impact of the deleted and inserted amino acid(s) is unknown at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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