Submissions for variant NM_002878.4(RAD51D):c.473_480+1del

dbSNP: rs786202819

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000165835	SCV000216582	uncertain significance	Hereditary cancer-predisposing syndrome	2024-12-05	criteria provided, single submitter	clinical testing	The c.473_480+1delAGGAACAGG alteration is a deletion beginning in coding exon 5 of the RAD51D gene and extending 1 nucleotide into intron 5. This results in the deletion of a total of 9 nucleotides, including the last 8 nucleotides of coding exon 5 and the first nucleotide of the splice donor site of intron 5. This nucleotide region is well conserved in available vertebrate species. In silico analysis predicts that this alteration will abolish the native splice donor site while creating a novel splice donor site. Usage of this novel donor site would result in an in-frame transcript with uncertain functional impact. RNA studies have also demonstrated that this alteration results in a transcript predicted to lead to a protein with an in-frame deletion of only 3 amino acids (Ambry internal data). The exact functional impact of the deleted amino acids are unknown at this time. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001066873	SCV001231896	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2024-02-24	criteria provided, single submitter	clinical testing	This variant, c.472_480del, results in the deletion of 3 amino acid(s) of the RAD51D protein (p.Glu158_Gln160del), but otherwise preserves the integrity of the reading frame. 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. This variant is also known as c.473_480+1del. ClinVar contains an entry for this variant (Variation ID: 186269). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Baylor Genetics	RCV001066873	SCV005054050	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 4	2023-11-02	criteria provided, single submitter	clinical testing
GeneDx	RCV004719726	SCV005326037	uncertain significance	not provided	2023-11-29	criteria provided, single submitter	clinical testing	Canonical splice site variant with an unclear effect on protein function; Not observed at significant frequency in large population cohorts (gnomAD); Observed in an individual with breast cancer (PMID: 32427313); This variant is associated with the following publications: (PMID: 14704354, 21111057, 19327148, 32427313)