ClinVar Miner

Submissions for variant NM_005591.3(MRE11):c.121G>A (p.Asp41Asn) (rs116679717)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212553 SCV000149813 likely 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 RCV000115904 SCV000172749 likely benign Hereditary cancer-predisposing syndrome 2018-12-18 criteria provided, single submitter clinical testing Subpopulation frequency in support of benign classification;in silico models in agreement (benign)
Invitae RCV000858639 SCV000260742 benign Ataxia-telangiectasia-like disorder 2019-12-29 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000313574 SCV000374945 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.
Counsyl RCV000313574 SCV000488768 likely benign Ataxia-telangiectasia-like disorder 1 2016-08-12 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000212553 SCV000604245 likely benign not specified 2017-01-24 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000212553 SCV000705276 benign not specified 2017-01-20 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000212553 SCV000919677 benign not specified 2018-05-11 criteria provided, single submitter clinical testing Variant summary: MRE11A c.121G>A (p.Asp41Asn) results in a conservative amino acid change located in the Calcineurin-like phosphoesterase domain, ApaH type of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00097 in 277088 control chromosomes in the gnomAD database, including 1 homozygotes. The observed variant frequency is approximately 15-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in MRE11A causing Hereditary Breast and Ovarian Cancer phenotype (6.3e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.121G>A in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign/benign" (5x) and "uncertain significance" (1x). Based on the evidence outlined above, the variant was classified as benign.

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