Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000131791 | SCV000186840 | likely benign | Hereditary cancer-predisposing syndrome | 2018-04-10 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Co-occurence with a mutation in another gene that clearly explains a proband's phenotype,In silico models in agreement (benign) |
| Invitae | RCV000657154 | SCV000283370 | likely benign | not provided | 2019-02-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000657154 | SCV000573397 | uncertain significance | not provided | 2018-06-27 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.9493A>G at the cDNA level, p.Thr3165Ala (T3165A) at the protein level, and results in the change of a Threonine to an Alanine (ACT>GCT). Using alternate nomenclature, this variant would be defined as BRCA2 9721A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Thr3165Ala was not observed at a significant frequency in large population cohorts (Lek 2016). This variant is located within the DNA binding domain (Yang 2002). In silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Thr3165Ala is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000483383 | SCV000600863 | uncertain significance | not specified | 2017-07-14 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000657154 | SCV000885111 | uncertain significance | not provided | 2017-07-31 | criteria provided, single submitter | clinical testing | |
| Color | RCV000131791 | SCV000911213 | likely benign | Hereditary cancer-predisposing syndrome | 2016-04-25 | criteria provided, single submitter | clinical testing | |
| Integrated Genetics/Laboratory Corporation of America | RCV000483383 | SCV000916939 | uncertain significance | not specified | 2019-07-01 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.9493A>G (p.Thr3165Ala) results in a non-conservative amino acid change located in the OB3 fold (IPR015188) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-05 in 251138 control chromosomes, predominantly at a frequency of 0.00038 within the Latino subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (5.2e-05 vs 0.00075), allowing no conclusion about variant significance. c.9493A>G has been reported in the literature in an individual with colorectal cancer (Ricker_2017) . This report does not provide an unequivocal conclusion 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. Six ClinVar submissions (evaluation after 2014) cite the variant three times as likely benign and three times as uncertian significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |