Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Spanish ATM Cancer Susceptibility Variant Interpretation Working Group | RCV001693497 | SCV001911467 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-06-17 | criteria provided, single submitter | clinical testing | The c.5373T>C (p.Asp1791=) variant is absent from the gnomAD v2.1.1 non-cancer dataset, in a position with adequate coverage (>20x) (PM2; http://gnomad.broadinstitute.org). It is a silent variant not predicted to lead to a splicing alteration as per SPiCE predictor and no splicing site is created/activated according to at least 3 splicing predictors of the set SpliceSiteFinderlike - MaxEntScan - NNSplice – GeneSplicer (BP4). The variant is located at a nucleotide that is not highly conserved across species, based on PhyloP (BP7). Therefore, this variant meets criteria to be classified as likely benign. Adapted ACMG/AMP rules applied as defined by the Spanish ATM working group: PM2 + BP4 + BP7 (PMID: 33280026). |
| Ambry Genetics | RCV001693497 | SCV003868795 | likely benign | Hereditary cancer-predisposing syndrome | 2023-01-14 | 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. |
| Myriad Genetics, |
RCV004591555 | SCV005084346 | benign | Familial cancer of breast | 2024-05-23 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. |