ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.950_954CAGAG[3] (p.Ala321fs) (rs771998974)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000579754 SCV000686504 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-25 criteria provided, single submitter clinical testing
GeneDx RCV000657484 SCV000779219 uncertain significance not provided 2018-03-12 criteria provided, single submitter clinical testing This duplication of five nucleotides in RAD51D is denoted c.955_959dupCAGAG at the cDNA level and p.Ala321ArgfsX32 (A321RfsX32) at the protein level. The normal sequence, with the bases that are duplicated in brackets, is AGAG[dupCAGAG]TGCC. The duplication causes a frameshift, which changes an Alanine to an Arginine at codon 321 in the last exon of the gene, and results in an extension of the protein. The last 8 correct amino acids are replaced by 31 incorrect ones, disrupting a region that contains the RAD51C binding domain (Miller 2004). RAD51D c.955_959dupCAGAG has not, to our knowledge, been reported in the literature. This variant was observed at an allele frequency of 0.026% (8/30,782) in individuals of South Asian ancestry in large population cohorts (Lek 2016). Since the clinical significance of this protein extension is unclear, we consider RAD51D c.955_959dupCAGAG to be a variant of uncertain significance.
Invitae RCV000528793 SCV000651796 uncertain significance Breast-ovarian cancer, familial 4 2017-07-31 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the RAD51D gene (p.Ala321Argfs*32). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 8 amino acids of the RAD51D protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with RAD51D-related disease. 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.

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