Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000166423 | SCV000217218 | likely benign | Hereditary cancer-predisposing syndrome | 2014-10-17 | 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 |
RCV000627775 | SCV000547423 | likely benign | Ataxia-telangiectasia-like disorder | 2025-01-23 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001762386 | SCV001989772 | uncertain significance | not provided | 2019-05-17 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987386 | SCV004803385 | benign | not specified | 2024-01-02 | criteria provided, single submitter | clinical testing | Variant summary: MRE11A c.1090C>A alters a conserved nucleotide resulting in a synonymous change. Consensus agreement among computation 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 6.7e-05 in 282770 control chromosomes, predominantly at a frequency of 0.0011 within the Ashkenazi Jewish subpopulation in the gnomAD database. The observed variant frequency within Ashkenazi Jewish control individuals in the gnomAD database is approximately 17-fold of the estimated maximal expected allele frequency for a pathogenic variant in MRE11A causing Hereditary Breast And Ovarian Cancer Syndrome phenotype (6.3e-05), strongly suggesting that the variant is a benign polymorphism. To our knowledge, no occurrence of c.1090C>A in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely benign, while the other submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign. |