Submissions for variant NM_058216.3(RAD51C):c.785T>A (p.Leu262Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002412231	SCV002669402	pathogenic	Hereditary cancer-predisposing syndrome	2022-05-02	criteria provided, single submitter	clinical testing	The p.L262* pathogenic mutation (also known as c.785T>A), located in coding exon 5 of the RAD51C gene, results from a T to A substitution at nucleotide position 785. This changes the amino acid from a leucine to a stop codon within coding exon 5. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003099762	SCV003327682	pathogenic	Fanconi anemia complementation group O	2022-03-12	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu262*) 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).