Submissions for variant NM_002878.4(RAD51D):c.263+5G>C

dbSNP: rs1567735224

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001761034	SCV001999831	uncertain significance	not provided	2021-10-27	criteria provided, single submitter	clinical testing	Intronic +5 splice site variant predicted to result in skipping of the adjacent exon 3; however, RNA studies demonstrate naturally occurring isoforms lacking exon 3 in multiple tissues (Davy 2017, Brandao 2019); Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek 2016)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001868496	SCV002193072	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2024-01-03	criteria provided, single submitter	clinical testing	This sequence change falls in intron 3 of the RAD51D gene. It does not directly change the encoded amino acid sequence of the RAD51D protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. ClinVar contains an entry for this variant (Variation ID: 1310864). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown this variant is associated with skipping of exon 3 and/or pseudo exon inclusion, but one or more of the resulting mRNA isoform(s) may be naturally occurring (Invitae). 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.
Color Diagnostics, LLC DBA Color Health	RCV003584980	SCV004357173	uncertain significance	Hereditary cancer-predisposing syndrome	2021-09-20	criteria provided, single submitter	clinical testing	This variant causes a G to C nucleotide substitution at the +5 position of intron 3 of the RAD51D gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although this prediction has not been confirmed in published RNA studies, this variant is predicted to result in a disrupted protein product. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.