Description
The RAD51C c.706-2A>G variant was identified in 12 of 15014 proband chromosomes (frequency: 0.0008) from individuals or families with breast and ovarian cancer (Castera 2014, Couch 2015, Golmard 2013, Loveday 2012, Song 2015). The variant was also identified in the following databases: dbSNP (ID: rs587780259) as "With Pathogenic allele", ClinVar (5x pathogenic, 2x likely pathogenic), Clinvitae, and LOVD 3.0 (1x). The variant was not identified in Cosmic or the MutDB database. The variant was identified in control databases in 6 of 277092 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017). It was observed in the European population in 6 of 126600 chromosomes (freq: 0.00005), but not in the African, Other, Latino, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. Functional studies utilizing mRNA from lymphoblastoid cell lines shows this variant affects splicing, resulting in in-frame skipping of exon 5 (Golmard 2013, Davy 2017). The c.706-2A>G variant is predicted to cause abnormal splicing because the nucleotide substitution occurs in the invariant region of the splice consensus sequence. In addition, 5 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. In summary, based on the above information this variant meets our laboratory’s criteria to be classified as pathogenic.
| # | Sample | Method | Observation |
|---|
| Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
|---|
| 1 | unknown | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |
