Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000636203 | SCV000757635 | likely benign | Familial cancer of breast; Fanconi anemia complementation group J | 2024-01-21 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781171 | SCV000919050 | likely benign | not specified | 2019-08-29 | criteria provided, single submitter | clinical testing | Variant summary: BRIP1 c.2907T>C (p.Asn969Asn) alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools (ALAMUT) predict no significant impact on normal splicing. Another in-silico tool for assessing the pathogenicity of synonymous variants, namely TraP (Transcript-inferred Pathogenicity, Gelfman_2017) predicts this variant to be benign. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 250176 control chromosomes (gnomAD). 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.2907T>C in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |
Ambry Genetics | RCV002438686 | SCV002746865 | likely benign | Hereditary cancer-predisposing syndrome | 2021-08-30 | 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, |
RCV004788061 | SCV005405466 | benign | Familial cancer of breast | 2024-09-09 | 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. |