Submissions for variant NM_058216.3(RAD51C):c.444del (p.Phe148fs)

dbSNP: rs1555594617

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000657413	SCV000779148	likely pathogenic	not provided	2017-11-14	criteria provided, single submitter	clinical testing	This deletion of one nucleotide in RAD51C is denoted c.444delT at the cDNA level and p.Phe148LeufsX23 (F148LfsX23) at the protein level. The normal sequence, with the base that is deleted in brackets, is GTTT[delT]GGAG. The deletion causes a frameshift which changes a Phenylalanine to a Leucine at codon 148, and creates a premature stop codon at position 23 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.
Color Diagnostics, LLC DBA Color Health	RCV001805783	SCV002052985	pathogenic	Hereditary cancer-predisposing syndrome	2021-06-08	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 3 of the RAD51C gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals undergoing genetic testing for hereditary cancer in the literature (DOI: 10.1101/2021.04.15.21255554). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of RAD51C function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001861680	SCV002216038	pathogenic	Fanconi anemia complementation group O	2022-08-21	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 545841). 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.Phe148Leufs*23) 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).