Submissions for variant NM_058216.3(RAD51C):c.622_623del (p.Ile208fs)

dbSNP: rs876659497

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000214716	SCV000276037	pathogenic	Hereditary cancer-predisposing syndrome	2015-05-27	criteria provided, single submitter	clinical testing	The c.622_623delAT pathogenic mutation, located in coding exon 4 of the RAD51C gene, results from a deletion of two nucleotides between nucleotide positions 622 and 623, causing a translational frameshift with a predicted alternate stop codon. This alteration was identified in one patient from a large study of 708 breast and/or ovarian patients (Castéra L, Eur. J. Hum. Genet. 2014 Nov; 22(11):1305-13). Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Invitae	RCV001382685	SCV001581585	pathogenic	Fanconi anemia complementation group O	2023-07-28	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with personal or family histories of breast and/or ovarian cancer (PMID: 24549055, 29255180). This variant is present in population databases (rs765883905, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Ile208Leufs*7) in the RAD51C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917, 29278735).
Hereditary Cancer Group, L’Institut d'Investigació Biomèdica de Bellvitge	RCV001778807	SCV001623536	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3	2021-05-03	criteria provided, single submitter	curation
Baylor Genetics	RCV001778807	SCV004208030	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3	2022-09-01	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV001778807	SCV004931417	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3	2024-01-03	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.