Submissions for variant NM_058216.3(RAD51C):c.910del (p.Ser304fs)

dbSNP: rs1555603011

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000523699	SCV000618331	likely pathogenic	not provided	2017-03-17	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in RAD51C is denoted c.910delA at the cDNA level and p.Ser304ValfsX10 (S304VfsX10) at the protein level. The normal sequence, with the base that is deleted in brackets, is GGAA[delA]GTTG. The deletion causes a frameshift which changes a Serine to a Valine at codon 304, and creates a premature stop codon at position 10 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, we consider this deletion to be a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000810547	SCV000950760	pathogenic	Fanconi anemia complementation group O	2020-04-12	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917). This variant has been observed in an individual affected with ovarian cancer (PMID: 29255180). ClinVar contains an entry for this variant (Variation ID: 449877). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ser304Valfs*10) in the RAD51C gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics	RCV002376963	SCV002685961	pathogenic	Hereditary cancer-predisposing syndrome	2021-11-01	criteria provided, single submitter	clinical testing	The c.910delA pathogenic mutation, located in coding exon 7 of the RAD51C gene, results from a deletion of one nucleotide at nucleotide position 910, causing a translational frameshift with a predicted alternate stop codon (p.S304Vfs*10). This alteration was identified in multiple individuals diagnosed with ovarian cancer (Golmard L et al. Eur J Hum Genet, 2017 12;25:1345-1353; Carter NJ et al. Gynecol Oncol, 2018 12;151:481-488). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.