Submissions for variant NM_058216.3(RAD51C):c.145+12T>G

gnomAD frequency: 0.00024  dbSNP: rs377297129

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000127693	SCV000171272	benign	not specified	2014-02-26	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Counsyl	RCV000410695	SCV000490071	likely benign	Fanconi anemia complementation group O	2016-10-25	criteria provided, single submitter	clinical testing
Counsyl	RCV000411797	SCV000490072	likely benign	Breast-ovarian cancer, familial, susceptibility to, 3	2016-10-25	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000579441	SCV000686326	likely benign	Hereditary cancer-predisposing syndrome	2015-09-03	criteria provided, single submitter	clinical testing
Mendelics	RCV000410695	SCV001140709	likely benign	Fanconi anemia complementation group O	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000410695	SCV001282773	uncertain significance	Fanconi anemia complementation group O	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV000411797	SCV001285751	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 3	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae	RCV000410695	SCV002349813	likely benign	Fanconi anemia complementation group O	2024-01-30	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000579441	SCV002531797	likely benign	Hereditary cancer-predisposing syndrome	2020-11-25	criteria provided, single submitter	curation
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000127693	SCV002551124	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149869	SCV003837694	likely benign	Breast and/or ovarian cancer	2021-11-05	criteria provided, single submitter	clinical testing
Leiden Open Variation Database	RCV001195010	SCV001365244	uncertain significance	not provided	2014-11-02	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Christine Rappaport.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354401	SCV001549011	likely benign	Malignant tumor of breast		no assertion criteria provided	clinical testing	The RAD51C c.145+12T>G variant was not identified in the literature or in Cosmic, MutDB, and LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs377297129) “With Likely benign allele”, ClinVar (classified as benign by GeneDx and likely benign by Counsyl), Clinvitae (3x), and in control databases in 39 of 276870 chromosomes at a frequency of 0.0001 increasing the likelihood that this may be a low frequency benign variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017); seen in the following populations: African in 1 of 24024 chromosomes (frequency: 0.00004), Latino in 1 of 34412 chromosomes (frequency: 0.00003), and European Non-Finnish in 37 of 126410 chromosomes (frequency: 0.0003). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV001195010	SCV001905995	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001195010	SCV001930004	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001195010	SCV001959215	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001195010	SCV001977674	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001195010	SCV001980054	likely benign	not provided		no assertion criteria provided	clinical testing