Submissions for variant NM_058216.3(RAD51C):c.181_182del (p.Leu61fs)

dbSNP: rs786203945

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000167466	SCV000218322	pathogenic	Hereditary cancer-predisposing syndrome	2023-02-07	criteria provided, single submitter	clinical testing	The c.181_182delCT pathogenic mutation, located in coding exon 2 of the RAD51C gene, results from a deletion of two nucleotides at nucleotide positions 181 to 182, causing a translational frameshift with a predicted alternate stop codon (p.L61Afs*11). This alteration, designated as c.179_180del, was identified in 1/692 men with metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis (Pritchard CC et al. N. Engl. J. Med., 2016 Aug;375:443-53). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000456496	SCV000550223	pathogenic	Fanconi anemia complementation group O	2024-01-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Leu61Alafs*11) 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). This variant is present in population databases (rs754525165, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with prostate cancer (PMID: 27433846). This variant is also known as c.179_180del. ClinVar contains an entry for this variant (Variation ID: 187716). For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000657321	SCV000779052	pathogenic	not provided	2023-01-25	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27433846, 27806231, 30947698, 32365798, 35220195, 29625052, 29922827, 32107557)
Color Diagnostics, LLC DBA Color Health	RCV000167466	SCV001340644	pathogenic	Hereditary cancer-predisposing syndrome	2021-12-14	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides in exon 2 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 males affected with breast cancer (PMID: 32365798) and metastatic prostate cancer (PMID: 27433846). This variant has been identified in 3/251400 chromosomes 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.
Revvity Omics, Revvity	RCV000456496	SCV002019635	pathogenic	Fanconi anemia complementation group O	2021-04-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004535139	SCV004113257	pathogenic	RAD51C-related disorder	2022-09-01	criteria provided, single submitter	clinical testing	The RAD51C c.181_182delCT variant is predicted to result in a frameshift and premature protein termination (p.Leu61Alafs*11). This variant (reported as c.179_180del) was identified in an individual affected with metastatic prostate cancer, and was classified as pathogenic (Table S1, Pritchard et al. 2016. PubMed ID: 27433846). This variant is reported in 0.0046% of alleles in individuals of European (Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/17-56772324-ACT-A) and has been interpreted as pathogenic in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/187716/). Frameshift variants in RAD51C are expected to be pathogenic. This variant is interpreted as pathogenic.
Baylor Genetics	RCV003468811	SCV004207935	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3	2024-02-29	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV003468811	SCV004930367	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 frameshift predicted to result in premature protein truncation.
Leiden Open Variation Database	RCV000657321	SCV001365248	pathogenic	not provided	2019-12-04	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Andreas Laner.