ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.263G>T (p.Ser88Ile)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000820986 SCV000961725 uncertain significance Breast-ovarian cancer, familial 4 2018-10-17 criteria provided, single submitter clinical testing This sequence change replaces serine with isoleucine at codon 88 of the RAD51D protein (p.Ser88Ile). The serine residue is moderately conserved and there is a large physicochemical difference between serine and isoleucine. This variant also falls at the last nucleotide of exon 3 of the RAD51D coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs757467813, ExAC 0.006%). This variant has not been reported in the literature in individuals with RAD51D-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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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