Submissions for variant NM_000059.4(BRCA2):c.*105A>C

gnomAD frequency: 0.15131  dbSNP: rs15869

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000112856	SCV000245315	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2015-01-12	reviewed by expert panel	curation	Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.229 (Asian), 0.01626 (African), 0.2124 (European), derived from 1000 genomes (2012-04-30).
Illumina Laboratory Services, Illumina	RCV000273093	SCV000383815	benign	Fanconi anemia complementation group D1	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	RCV000112856	SCV000383816	benign	Breast-ovarian cancer, familial, susceptibility to, 2	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.
GeneKor MSA	RCV000585691	SCV000693649	benign	not specified	2017-11-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000112856	SCV000743532	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2014-10-09	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811401	SCV000883471	benign	not provided	2023-11-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002319438	SCV002608658	benign	Hereditary cancer-predisposing syndrome	2014-11-19	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.
Breakthrough Genomics, Breakthrough Genomics	RCV001811401	SCV005236567	benign	not provided		criteria provided, single submitter	not provided
Breast Cancer Information Core (BIC) (BRCA2)	RCV000112856	SCV000145775	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2010-12-17	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000585691	SCV001548650	benign	not specified		no assertion criteria provided	clinical testing	#N/A
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV000585691	SCV001906326	benign	not specified		no assertion criteria provided	clinical testing