Submissions for variant NM_058216.3(RAD51C):c.967T>C (p.Leu323=)

gnomAD frequency: 0.00006  dbSNP: rs747727600

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163204	SCV000213726	likely benign	Hereditary cancer-predisposing syndrome	2014-08-11	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV001721040	SCV000525773	likely benign	not provided	2019-10-08	criteria provided, single submitter	clinical testing
Invitae	RCV000475036	SCV000560779	likely benign	Fanconi anemia complementation group O	2023-12-24	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163204	SCV000686410	likely benign	Hereditary cancer-predisposing syndrome	2015-10-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000430391	SCV001338207	likely benign	not specified	2020-02-17	criteria provided, single submitter	clinical testing	Variant summary: RAD51C c.967T>C (p.Leu323Leu) alters a non-conserved 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: Three predict the variant abolishes a 3' acceptor site. The Transcript-inferred Pathogenicity (TrAP) score predicts the variant to be benign. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 251372 control chromosomes. 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.967T>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.
Sema4, Sema4	RCV000163204	SCV002530040	likely benign	Hereditary cancer-predisposing syndrome	2022-02-07	criteria provided, single submitter	curation
GenomeConnect, ClinGen	RCV001249246	SCV001423183	not provided	Breast-ovarian cancer, familial, susceptibility to, 3		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 10-30-2018 by Lab or GTR ID North York General. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.