Submissions for variant NM_002878.4(RAD51D):c.82+5_82+13delinsT

dbSNP: rs2091796708

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001181085	SCV001346161	uncertain significance	Hereditary cancer-predisposing syndrome	2020-02-21	criteria provided, single submitter	clinical testing	This variant causes a deletion of 8 nucleotides from intron 1 splice donor site of the RAD51D gene. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001194376	SCV001363867	uncertain significance	not specified	2019-02-20	criteria provided, single submitter	clinical testing	Variant summary: RAD51D c.82+5_82+13delinsT alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a cryptic 5 donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 240122 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.82+5_82+13delinsT in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrences with other pathogenic variant(s) have been reported (BRCA2 c.4037_4038delCT, p.Thr1346fsX5), providing supporting evidence for a benign role. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics	RCV001181085	SCV002679711	uncertain significance	Hereditary cancer-predisposing syndrome	2024-12-10	criteria provided, single submitter	clinical testing	The c.82+5_82+13delCCGGGTGTGinsT intronic variant, located downstream of coding exon 1 in the RAD51D gene, results from a deletion of 9 nucleotides and the insertion of 1 nucleotide at positions c.82+5 to c.82+13. This nucleotide region is not well conserved in available vertebrate species. In silico splice site analysis for this alteration is inconclusive and direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.