ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.732del (p.Ile244fs) (rs1060502601)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471345 SCV000550222 pathogenic Fanconi anemia, complementation group O 2019-11-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ile244Metfs*9) in the RAD51C gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in two individuals affected with ovarian cancer (PMID: 26261251, 26720728). This variant is also known as c.731delT in the literature. ClinVar contains an entry for this variant (Variation ID: 409860). Loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000486595 SCV000569471 likely pathogenic not provided 2016-04-08 criteria provided, single submitter clinical testing This deletion of one nucleotide in RAD51C is denoted c.732delT at the cDNA level and p.Ile244MetfsX9 (I244MfsX9) at the protein level. The normal sequence, with the base that is deleted in braces, is GTAT[T]GCTT. The deletion causes a frameshift which changes an Isoleucine to a Methionine at codon 244, and creates a premature stop codon at position 9 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. RAD51C c.732delT, also known as 731delT using alternate nomenclature, has been observed in at least two individuals with a personal and family history of ovarian and/or breast cancer (Song 2015). Based on the currently available information, we consider this deletion to be a likely pathogenic variant.
Counsyl RCV000576324 SCV000677833 pathogenic Breast-ovarian cancer, familial 3; Fanconi anemia, complementation group O 2017-03-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589098 SCV000699821 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-12-16 criteria provided, single submitter clinical testing Variant summary: The RAD51C c.732delT (p.Ile244Metfs) variant results in a premature termination codon, predicted to cause a truncated or absent RAD51C protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/130846 control chromosomes at a frequency of 0.0000076, which does not exceed the estimated maximal expected allele frequency of a pathogenic RAD51C variant (0.0000625). The variant was reported in two affected individuals and one control individual from the literature (Song_2015, Norquist_2016). While this variant is predicted to be pathogenic, more clinical or functional data is needed to definitively classify this variant as pathogenic. Taken together, this variant is classified as likely pathogenic.
Color RCV000775758 SCV000910195 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Ambry Genetics RCV000775758 SCV001188627 pathogenic Hereditary cancer-predisposing syndrome 2017-12-21 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)

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