Submissions for variant NM_002878.4(RAD51D):c.346-1G>C

dbSNP: rs1555568386

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000564788	SCV000671965	likely pathogenic	Hereditary cancer-predisposing syndrome	2023-10-12	criteria provided, single submitter	clinical testing	The c.346-1G>C intronic variant results from a G to C substitution one nucleotide upstream from coding exon 5 of the RAD51D gene. This nucleotide position is highly conserved in available vertebrate species. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001858346	SCV002249418	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 4	2024-05-21	criteria provided, single submitter	clinical testing	This sequence change affects an acceptor splice site in intron 4 of the RAD51D gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in RAD51D are known to be pathogenic (PMID: 21822267). 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: 484788). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001858346	SCV003804687	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 4	2023-05-16	criteria provided, single submitter	clinical testing	Criteria applied: PVS1,PS4_MOD,PM2_SUP
Myriad Genetics, Inc.	RCV001858346	SCV004931492	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 4	2024-01-04	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant occurs within a consensus splice junction and is predicted to result in abnormal mRNA splicing of either an out-of-frame exon or an in-frame exon necessary for protein stability and/or normal function.