Submissions for variant NM_002878.4(RAD51D):c.215del (p.Tyr72fs)

dbSNP: rs2142474090

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001389724	SCV001591176	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 4	2022-07-19	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr72Serfs*4) in the RAD51D gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD51D are known to be pathogenic (PMID: 21822267). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1075993). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. This variant is not present in population databases (gnomAD no frequency).
Hereditary Cancer Group, L’Institut d'Investigació Biomèdica de Bellvitge	RCV001788468	SCV001712118	pathogenic	Deleterious RAD51D Gene Mutation	2021-06-08	criteria provided, single submitter	clinical testing
GeneDx	RCV002291756	SCV002584328	uncertain significance	not provided	2022-04-11	criteria provided, single submitter	clinical testing	Frameshift variant in exon 3 predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; however RNA studies demonstrate a naturally occurring isoform lacking exon 3 in multiple tissues (Davy 2017, Brandao 2019); Not observed at significant frequency in large population cohorts (gnomAD); Observed in an individual with pancreatic cancer (Boni 2021); This variant is associated with the following publications: (PMID: 28905878, 30623411, 34923718)
Fulgent Genetics, Fulgent Genetics	RCV001389724	SCV002777719	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 4	2021-12-20	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV001389724	SCV004931074	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 4	2024-01-04	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.