ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.571+4A>G (rs587780257)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000116176 SCV000185236 likely benign Hereditary cancer-predisposing syndrome 2017-09-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,RNA Studies
Color RCV000116176 SCV000691250 uncertain significance Hereditary cancer-predisposing syndrome 2018-06-19 criteria provided, single submitter clinical testing
Counsyl RCV000662721 SCV000785476 uncertain significance Breast-ovarian cancer, familial 3; Fanconi anemia, complementation group O 2017-08-22 criteria provided, single submitter clinical testing
GeneDx RCV000212940 SCV000150085 uncertain significance not provided 2018-04-20 criteria provided, single submitter clinical testing This variant is denoted RAD51C c.571+4A>G or IVS3+4A>G and consists of an A>G nucleotide substitution at the +4 position of intron 3 of the RAD51C gene. In-silico analysis, which includes splice predictors and evolutionary conservation, supports a deleterious effect. However, in the absence of RNA or functional studies, the actual effect of this variant is unknown. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. This variant was not observed in large population cohorts (Lek 2016). Based on currently available evidence, it is unclear whether RAD51C c.571+4A>G is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000206409 SCV000261422 uncertain significance Fanconi anemia, complementation group O 2018-12-21 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the RAD51C gene. It does not directly change the encoded amino acid sequence of the RAD51C protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with breast cancer (PMID: 26845104). ClinVar contains an entry for this variant (Variation ID: 128207). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). An experimental study using RT-PCR has reported that this variant affects RNA splicing and results in the skipping of exon 3 (PMID: 26845104). 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.
Mendelics RCV000709506 SCV000839330 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine,University of Washington RCV000116176 SCV000266229 uncertain significance Hereditary cancer-predisposing syndrome 2015-11-20 criteria provided, single submitter clinical testing This variant is predicted to alter a splice donor site. RT-PCR confirmed this variant causes exon 3 skipping.

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