ClinVar Miner

Submissions for variant NM_058216.3(RAD51C):c.774del (p.Thr259fs) (rs754367349)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484016 SCV000566828 likely pathogenic not provided 2017-04-24 criteria provided, single submitter clinical testing This deletion of one nucleotide in RAD51C is denoted c.774delT at the cDNA level and p.Thr259LeufsX4 (T259LfsX4) at the protein level. The normal sequence, with the base that is deleted in brackets, is TTCG[delT]ACTC. The deletion causes a frameshift which changes a Threonine to a Leucine at codon 259, and creates a premature stop codon at position 4 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.774delT has been observed in multiple women with personal and family histories of breast and/or ovarian cancer and has been suggested to be a recurrent variant in the Swedish population (Sopik 2014, Osorio 2012, Romero 2011, Vuorela 2011, Cunningham 2014, Song 2015). Based on the currently available information, we consider this deletion to be a likely pathogenic variant.
Counsyl RCV000576452 SCV000677785 pathogenic Breast-ovarian cancer, familial 3; Fanconi anemia, complementation group O 2017-02-14 criteria provided, single submitter clinical testing
Color RCV000581899 SCV000691266 pathogenic Hereditary cancer-predisposing syndrome 2017-09-29 criteria provided, single submitter clinical testing
Invitae RCV000697930 SCV000826564 pathogenic Fanconi anemia, complementation group O 2019-12-31 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr259Leufs*4) in the RAD51C gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs754367349, ExAC 0.02%). This variant has been reported in individuals affected with breast cancer (PMID: 21537932, 26261251) and an individual affected with ovarian cancer (PMID: 21750962). ClinVar contains an entry for this variant (Variation ID: 419188). 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.
Ambry Genetics RCV000581899 SCV001189230 pathogenic Hereditary cancer-predisposing syndrome 2019-04-05 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Rarity in general population databases (dbsnp, esp, 1000 genomes)
Leiden Open Variation Database RCV000484016 SCV001365275 pathogenic not provided 2020-02-28 no assertion criteria provided curation Curator: Arleen D. Auerbach. Submitter to LOVD: Johan den Dunnen.

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