Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000222216 | SCV000275040 | likely benign | Hereditary cancer-predisposing syndrome | 2015-04-01 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
Gene |
RCV001722185 | SCV000512289 | likely benign | not provided | 2020-12-24 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 18273839, 23893897, 29280214) |
Invitae | RCV000533270 | SCV000635817 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-01-03 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000222216 | SCV000682995 | likely benign | Hereditary cancer-predisposing syndrome | 2016-12-06 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000438203 | SCV000918725 | likely benign | not specified | 2018-04-06 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.1878A>G alters a non-conserved nucleotide resulting in a synonymous change. Several computational tools predict an impact on normal splicing: Three predict the variant creates a 5 donor site. However, multiple functional studies found the variant to not affect splicing (Anczukow_2008, Baert_2018). The variant was observed with an allele frequency of 5.1e-05 in 277002 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in BRCA1 causing Hereditary Breast and Ovarian Cancer (5.1e-05 vs 0.001), allowing no conclusion about variant significance. The variant, c.1878A>G, has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant predominantly as "likely benign" and one as "uncertain significance." Based on the evidence outlined above, the variant was classified as "likely benign." |
Illumina Laboratory Services, |
RCV001125931 | SCV001285068 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |