Submissions for variant NM_058216.3(RAD51C):c.250A>T (p.Lys84Ter)

dbSNP: rs1555593616

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000535884	SCV000660361	pathogenic	Fanconi anemia complementation group O	2023-08-14	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. RNA analysis performed to evaluate the impact of this premature translational stop signal on mRNA splicing indicates it does not significantly alter splicing (Invitae). ClinVar contains an entry for this variant (Variation ID: 478609). 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.Lys84*) 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).
Ambry Genetics	RCV000573983	SCV000663757	pathogenic	Hereditary cancer-predisposing syndrome	2024-01-08	criteria provided, single submitter	clinical testing	The p.K84* pathogenic mutation (also known as c.250A>T), located in coding exon 2 of the RAD51C gene, results from an A to T substitution at nucleotide position 250. This changes the amino acid from a lysine to a stop codon within coding exon 2. 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.
Color Diagnostics, LLC DBA Color Health	RCV000573983	SCV001353129	pathogenic	Hereditary cancer-predisposing syndrome	2021-04-22	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 2 of the RAD51C gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. 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.
Fulgent Genetics, Fulgent Genetics	RCV002497205	SCV002809745	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3; Fanconi anemia complementation group O	2024-04-17	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003459268	SCV004208024	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3	2022-10-21	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003459268	SCV004931646	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3	2024-01-02	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.