Submissions for variant NM_024529.5(CDC73):c.1185A>G (p.Gln395=)

gnomAD frequency: 0.00511  dbSNP: rs116358657

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001082568	SCV000290763	benign	Parathyroid carcinoma	2024-02-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589443	SCV000699509	benign	not provided	2016-04-28	criteria provided, single submitter	clinical testing	Variant summary: The c.1185A>G in CDC73 gene is a synonymous change that involves a non-conserved nucleotide. 5/5 splice-site tools in Alamut predict that this variant does not affect normal splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in the control population dataset of ExAC at frequency of 0.16%, predominantly in individuals of African descent (1.7%), including one homozygote. The observed frequency greatly exceeds the maximum expected allele frequency for a pathogenic variant of 0.00041%, suggesting that it is a benign polymorphism. The variant of interest has been reported polymorphism in published report(s) (Newey, 2010). Taken together, based on the prevalence in general population the variant was classified as Benign.
Ambry Genetics	RCV001010209	SCV001170368	likely benign	Hereditary cancer-predisposing syndrome	2018-10-01	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Illumina Laboratory Services, Illumina	RCV001099297	SCV001255740	likely benign	Hyperparathyroidism 1	2018-01-13	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001082568	SCV001255741	benign	Parathyroid carcinoma	2018-01-13	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	RCV001099298	SCV001255742	benign	Hyperparathyroidism 2 with jaw tumors	2018-01-13	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.
GeneDx	RCV000589443	SCV001751466	benign	not provided	2018-09-17	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 20052758)
Genetic Services Laboratory, University of Chicago	RCV001820766	SCV002066375	benign	not specified	2021-04-02	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001099298	SCV004016989	benign	Hyperparathyroidism 2 with jaw tumors	2023-07-07	criteria provided, single submitter	clinical testing