Submissions for variant NM_005591.4(MRE11):c.1994+10G>A

gnomAD frequency: 0.01130  dbSNP: rs1805366

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079590	SCV000262321	benign	Ataxia-telangiectasia-like disorder	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000298889	SCV000374922	benign	Ataxia-telangiectasia-like disorder 1	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	RCV000298889	SCV000488656	benign	Ataxia-telangiectasia-like disorder 1	2016-06-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586722	SCV000698606	benign	not provided	2017-08-16	criteria provided, single submitter	clinical testing	Variant summary: c.1994+10G>A in MRE11A gene is an intronic change that involves a non-conserved nucleotide. 4/5 programs in Alamut predict that this variant does not affect a 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 0.00317 (384/121126 chrs tested), predominantly in individuals of African descent (0.03533; 366/ 10360 chrs tested). The observed frequency exceeds the maximum expected allele frequency for a pathogenic variant of 0.0000625, suggesting that it is a common polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals in published reports but is cited as Likely Benign/Benign by reputable databases/clinical laboratory. Taking together, the variant was classified as Benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000298889	SCV001472666	benign	Ataxia-telangiectasia-like disorder 1	2021-05-08	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV001289102	SCV001476697	benign	not specified	2020-06-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000586722	SCV001851146	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225508	SCV002504799	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001289102	SCV002774030	benign	not specified	2021-08-03	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000298889	SCV004015916	benign	Ataxia-telangiectasia-like disorder 1	2023-07-07	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000586722	SCV002033991	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001289102	SCV002035285	benign	not specified		no assertion criteria provided	clinical testing