ClinVar Miner

Submissions for variant NM_005591.3(MRE11):c.120C>T (p.Leu40=) (rs1805364)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000160575 SCV000213020 likely benign Hereditary cancer-predisposing syndrome 2014-08-29 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000524512 SCV000745567 likely benign Ataxia-telangiectasia-like disorder 1 2017-06-28 criteria provided, single submitter clinical testing
GeneDx RCV000212552 SCV000211161 benign not specified 2013-11-06 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.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000524512 SCV000744083 likely benign Ataxia-telangiectasia-like disorder 1 2017-01-04 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,VU University Medical Center Amsterdam RCV000524512 SCV000746007 likely benign Ataxia-telangiectasia-like disorder 1 2016-01-24 no assertion criteria provided clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000212552 SCV000917681 benign not specified 2018-12-21 criteria provided, single submitter clinical testing Variant summary: The variant MRE11A c.120C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00055 in 277082 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 9-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). However, it does need to be noted that there is a pseudogene present on chromosome 3. The variant c.120C>T has been reported in the literature in individuals affected with breast cancer (Damiola_2014, Young_2016). These reports however do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000524512 SCV000253440 likely benign Ataxia-telangiectasia-like disorder 1 2017-12-28 criteria provided, single submitter clinical testing

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