Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000562529 | SCV000660463 | likely benign | Hereditary cancer-predisposing syndrome | 2019-10-15 | 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. |
| Color Diagnostics, |
RCV000562529 | SCV000687579 | likely benign | Hereditary cancer-predisposing syndrome | 2016-02-23 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000628184 | SCV000749077 | likely benign | Ataxia-telangiectasia syndrome | 2024-01-19 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000628184 | SCV000799962 | uncertain significance | Ataxia-telangiectasia syndrome | 2018-05-14 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194330 | SCV001363787 | uncertain significance | not specified | 2019-11-11 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.4909+3G>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. One computational tool predicts that the variant strengthens a 5 donor site. However, this prediction have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 251304 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4909+3G>A has been reported in the literature in an individual affected with colorectal cancer (Yurgelun_2017). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, 3 classifying the variant as VUS, and 1 calling it as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Gene |
RCV001584367 | SCV001819323 | uncertain significance | not provided | 2020-02-11 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In-silico analysis 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.; Observed in individuals with a personal history of colorectal cancer in published literature (Yurgelun 2017); This variant is associated with the following publications: (PMID: 28135145) |
| Myriad Genetics, |
RCV004592611 | SCV005083685 | benign | Familial cancer of breast | 2024-05-21 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant is intronic and is not expected to impact mRNA splicing. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752]. |
| Institute of Immunology and Genetics Kaiserslautern | RCV004669045 | SCV005093840 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2024-07-17 | criteria provided, single submitter | clinical testing | ACMG Criteria: PM2_p, BP5; Variant was found in heterozygous state |