Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000425170 | SCV000518184 | likely benign | not specified | 2017-10-30 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Invitae | RCV000457118 | SCV000560398 | likely benign | Hereditary breast ovarian cancer syndrome | 2023-10-14 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000580477 | SCV000683531 | likely benign | Hereditary cancer-predisposing syndrome | 2016-03-28 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000425170 | SCV001338005 | uncertain significance | not specified | 2020-01-06 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.316+18G>A 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. 5/5 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 8.1e-06 in 245526 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.316+18G>A has been reported in the literature in at least one individual affected with Breast Cancer (e.g. Tabarestani_2017) without strong evidence for causality. This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cited the variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |