Submissions for variant NM_058216.3(RAD51C):c.90G>A (p.Ala30=)

gnomAD frequency: 0.01193  dbSNP: rs115414895

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129170	SCV000183903	benign	Hereditary cancer-predisposing syndrome	2014-11-25	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000232678	SCV000291254	benign	Fanconi anemia complementation group O	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000412339	SCV000404317	benign	Breast-ovarian cancer, familial, susceptibility to, 3	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000232678	SCV000404318	benign	Fanconi anemia complementation group O	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Counsyl	RCV000232678	SCV000489825	benign	Fanconi anemia complementation group O	2016-05-25	criteria provided, single submitter	clinical testing
Counsyl	RCV000412339	SCV000489826	benign	Breast-ovarian cancer, familial, susceptibility to, 3	2016-05-25	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000129170	SCV000686403	benign	Hereditary cancer-predisposing syndrome	2015-04-20	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000508578	SCV000807183	benign	not specified	2016-10-03	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000508578	SCV000888607	benign	not specified	2020-12-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000759338	SCV001157634	benign	not provided	2022-03-09	criteria provided, single submitter	clinical testing
GeneDx	RCV000759338	SCV001862301	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000508578	SCV002551123	benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149887	SCV003838369	benign	Breast and/or ovarian cancer	2022-05-04	criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000412339	SCV004019898	benign	Breast-ovarian cancer, familial, susceptibility to, 3	2023-04-05	criteria provided, single submitter	clinical testing	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing.
Breakthrough Genomics, Breakthrough Genomics	RCV000759338	SCV005252833	benign	not provided		criteria provided, single submitter	not provided
True Health Diagnostics	RCV000129170	SCV000788203	likely benign	Hereditary cancer-predisposing syndrome	2017-10-10	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000508578	SCV001549665	benign	not specified		no assertion criteria provided	clinical testing	The RAD51C p.Ala30= variant was identified in the literature, however the frequency of this variant in an affected population was not provided and the variant is listed as a polymorphism (Rodriguez-Lopez 2004). The variant was also identified in the following databases: dbSNP (ID: rs115414895) as "With Likely benign allele", ClinVar (6x benign, 2x likely benign), and Clinvitae. The variant was not identified in Cosmic, MutDB, or the LOVD 3.0 database. The variant was identified in control databases in 1015 of 277216 chromosomes (16 homozygous) at a frequency of 0.004 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: African in 967 of 24030 chromosomes (freq: 0.04), Other in 6 of 6468 chromosomes (freq: 0.001), Latino in 34 of 34416 chromosomes (freq: 0.001), European in 5 of 126716 chromosomes (freq: 0.00004), and South Asian in 3 of 30782 chromosomes (freq: 0.0001). The variant was not observed in the Ashkenazi Jewish, East Asian, or Finnish populations. The p.Ala30= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000508578	SCV001906445	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000508578	SCV001958590	benign	not specified		no assertion criteria provided	clinical testing