ClinVar Miner

Submissions for variant NM_002878.3(RAD51D):c.738+3G>A (rs751062153)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000569209 SCV000663822 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-17 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
GeneDx RCV000609483 SCV000725304 likely benign not specified 2017-11-27 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000609483 SCV000918138 uncertain significance not specified 2017-12-04 criteria provided, single submitter clinical testing Variant summary: The RAD51D c.738+3G>A variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 3/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 4/235100 control chromosomes at a frequency of 0.000017, which does not exceed the estimated maximal expected allele frequency of a pathogenic RAD51D variant (0.000125). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories, nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS) until additional information becomes available.
Invitae RCV001210674 SCV001382172 uncertain significance Breast-ovarian cancer, familial 4 2019-11-11 criteria provided, single submitter clinical testing This sequence change falls in intron 8 of the RAD51D gene. It does not directly change the encoded amino acid sequence of the RAD51D protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs751062153, ExAC 0.02%). This variant has not been reported in the literature in individuals with RAD51D-related conditions. ClinVar contains an entry for this variant (Variation ID: 480529). 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 is not likely to affect RNA splicing, 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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