Submissions for variant NM_005591.4(MRE11):c.1032T>G (p.Leu344=)

gnomAD frequency: 0.00960  dbSNP: rs11020793

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000129049	SCV000183744	benign	Hereditary cancer-predisposing syndrome	2014-12-17	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
GeneDx	RCV000212565	SCV000211160	benign	not specified	2014-01-09	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.
Invitae	RCV001081395	SCV000261668	benign	Ataxia-telangiectasia-like disorder	2024-01-31	criteria provided, single submitter	clinical testing
Counsyl	RCV000410736	SCV000488849	benign	Ataxia-telangiectasia-like disorder 1	2016-07-12	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586471	SCV000698600	benign	not provided	2017-07-06	criteria provided, single submitter	clinical testing	Variant summary: The MRE11A c.1032T>G (p.Leu344Leu) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change located in the Mre11, DNA-binding (IPR007281) (InterPro). One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant of interest has been found in a large, broad control population, ExAC in 321/121170 control chromosomes (9 homozygotes) at a frequency of 0.0026492, which is approximately 42 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. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000410736	SCV001471736	benign	Ataxia-telangiectasia-like disorder 1	2022-10-21	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000212565	SCV001476692	benign	not specified	2020-02-20	criteria provided, single submitter	clinical testing
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV002225423	SCV002504819	benign	Hereditary breast ovarian cancer syndrome	2022-04-19	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000212565	SCV002774022	benign	not specified	2021-04-02	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000410736	SCV004015919	benign	Ataxia-telangiectasia-like disorder 1	2023-07-07	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003905227	SCV004718861	benign	MRE11-related condition	2019-06-27	criteria provided, single submitter	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).
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000212565	SCV001806975	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000212565	SCV001967598	benign	not specified		no assertion criteria provided	clinical testing