ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.1A>G (p.Met1Val) (rs561425038)

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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 RCV000574809 SCV000663826 pathogenic Hereditary cancer-predisposing syndrome 2017-05-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other acmg-defined mutation (i.e. initiation codon or gross deletion)
Counsyl RCV000576367 SCV000677796 likely pathogenic Breast-ovarian cancer, familial 4 2017-04-06 criteria provided, single submitter clinical testing
GeneDx RCV000505741 SCV000149719 likely pathogenic not provided 2016-11-28 criteria provided, single submitter clinical testing This variant alters the initiator Methionine codon, and the resultant protein would be described as “p.Met1?” to signify that it is not known if the loss of Met1 prevents all protein translation or if an abnormal protein is produced using an alternate Methionine codon. RAD51D c.1A>G has not been previously published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. However, RAD51D c.1A>T, a different nucleotide change at the same position that also results in p.Met1?, has been reported in an individual with a personal history of both breast and ovarian cancer (Gutierrez-Enriquez 2014). As RAD51D c.1A>G is predicted to alter normal protein production, it is considered to be a likely pathogenic variant.
Invitae RCV000576367 SCV000932158 uncertain significance Breast-ovarian cancer, familial 4 2018-11-11 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the RAD51D mRNA. The next in-frame methionine is located at codon 16 in exon 1. This variant is present in population databases (rs561425038, ExAC 0.01%). This variant has been reported in an individual affected with ovarian cancer and colon polyps (PMID: 26681312) and an individual affected with colon cancer (PMID: 27978560). ClinVar contains an entry for this variant (Variation ID: 127884). Experimental studies have not been reported for this initiation codon variant and it is currently unknown if translation is rescued by either an in-frame or out-of-frame methionine. 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 RCV000709462 SCV000839206 likely pathogenic Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing

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