Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000557247 | SCV000622615 | uncertain significance | Ataxia-telangiectasia syndrome | 2022-09-15 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 37 of the ATM gene. It does not directly change the encoded amino acid sequence of the ATM protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs780204400, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 453596). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Color Diagnostics, |
RCV000583627 | SCV000687635 | likely benign | Hereditary cancer-predisposing syndrome | 2017-05-22 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001293568 | SCV001482173 | uncertain significance | not specified | 2021-02-12 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.5674+6C>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 8e-06 in 249250 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.5674+6C>G in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Center for Genomic Medicine, |
RCV001293568 | SCV004027242 | likely benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV005049588 | SCV005676477 | uncertain significance | Familial cancer of breast; Ataxia-telangiectasia syndrome | 2024-02-22 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000557247 | SCV002084985 | uncertain significance | Ataxia-telangiectasia syndrome | 2020-02-07 | no assertion criteria provided | clinical testing |