ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.270_271dup (p.Lys91fs) (rs753862052)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000570770 SCV000663808 pathogenic Hereditary cancer-predisposing syndrome 2017-11-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Color RCV000570770 SCV000686437 pathogenic Hereditary cancer-predisposing syndrome 2015-04-22 criteria provided, single submitter clinical testing
Counsyl RCV000226442 SCV000677792 likely pathogenic Breast-ovarian cancer, familial 4 2017-05-02 criteria provided, single submitter clinical testing
GeneDx RCV000657171 SCV000778892 pathogenic not provided 2017-11-15 criteria provided, single submitter clinical testing This duplication of 2 nucleotides is denoted RAD51D c.270_271dupTA at the cDNA level and p.Lys91IlefsX13 (K91IfsX13) at the protein level. The normal sequence, with the bases that are duplicated in brackets, is TTGA[dupTA]AACT. The duplication causes a frameshift, which changes a Lysine to an Isoleucine at codon 91, and creates a premature stop codon at position 13 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. RAD51D 270_271dupTA has been observed in at least one woman with a personal history of both breast and ovarian cancer, one man with breast cancer, and one unaffected individual with a family history of breast and ovarian cancer (Loveday 2011, Frey 2015, Pritzlaff 2017). We consider this variant to be pathogenic.
Invitae RCV000226442 SCV000287703 pathogenic Breast-ovarian cancer, familial 4 2018-11-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys91Ilefs*13) in the RAD51D gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs753862052, ExAC 0.1%). This variant has been reported in an individual with ovarian and breast cancer (PMID: 21822267), and an individual with male breast cancer (PMID: 28008555). ClinVar contains an entry for this variant (Variation ID: 239394). Loss-of-function variants in RAD51D are known to be pathogenic (PMID: 21822267). For these reasons, this variant has been classified as Pathogenic.

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