Submissions for variant NM_005591.4(MRE11):c.771A>G (p.Glu257=)

gnomAD frequency: 0.00301  dbSNP: rs13447632

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000212560	SCV000211156	benign	not specified	2014-02-05	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.
Ambry Genetics	RCV000160571	SCV000213105	likely benign	Hereditary cancer-predisposing syndrome	2014-08-18	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080782	SCV000252800	benign	Ataxia-telangiectasia-like disorder	2025-02-03	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000212560	SCV000336749	benign	not specified	2015-11-18	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586751	SCV000698609	benign	not provided	2017-07-21	criteria provided, single submitter	clinical testing	Variant summary: The MRE11A c.771A>G (p.Glu257Glu) variant involves the alteration of a non-conserved nucleotide causing a synonymous change and 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant does not affect ESE binding. However, these predictions have yet to be confirmed by functional studies. This variant was found in 281/276646 (2 homozygotes) control chromosomes at a frequency of 0.0010157, which is approximately 16 times the estimated maximal expected allele frequency of a pathogenic MRE11A variant (0.0000625), suggesting this variant is likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001112690	SCV001270378	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001112690	SCV001474090	benign	Ataxia-telangiectasia-like disorder 1	2023-11-06	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225463	SCV002504821	likely benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000160571	SCV002538432	benign	Hereditary cancer-predisposing syndrome	2021-03-08	criteria provided, single submitter	curation
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000212560	SCV002774027	benign	not specified	2021-09-17	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001112690	SCV004015926	benign	Ataxia-telangiectasia-like disorder 1	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000586751	SCV005213315	likely benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV003927528	SCV004755790	benign	MRE11-related disorder	2019-12-10	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).