Total submissions: 12
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001083475 | SCV000073755 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-01-05 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000130150 | SCV000184984 | likely benign | Hereditary cancer-predisposing syndrome | 2018-10-26 | 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 |
RCV000590167 | SCV000517839 | likely benign | not provided | 2021-05-04 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 25348012, 19043619, 25925381, 24817641, 29641532) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000440778 | SCV000695216 | likely benign | not specified | 2020-10-12 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.9190G>A (p.Asp3064Asn) results in a conservative amino acid change located in the BRCA2, OB3 domain (IPR015188) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251296 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.9190G>A has been reported in the literature in patients undergoing testing without information on cancer phenotype and in the UK10K cohort of control individuals collected as part of non-cancer studies (example, Qian_2018, Pritchard_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Furthermore, a computational method that produces a probabilistic likelihood ratio has reported this variant as having a neutral outcome (Karchin_2008). At-least one co-occurrence with another pathogenic variant has been reported at our laboratory (BRCA2 c.6408_6414delAAATGTT, p.N2137fs*29), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation reporting a majority consensus towards a benign/likely benign outcome (n=5). Some submitters cite overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was re-classified as likely benign. |
| Counsyl | RCV000077462 | SCV000786192 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2018-03-21 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000130150 | SCV000911250 | benign | Hereditary cancer-predisposing syndrome | 2016-12-19 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000590167 | SCV002047258 | likely benign | not provided | 2021-04-16 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV000590167 | SCV002048029 | uncertain significance | not provided | 2020-11-05 | criteria provided, single submitter | clinical testing | The BRCA2 c.9190G>A; p.Asp3064Asn variant (rs80359177), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 52772). This variant is found on only five chromosomes (5/282678 alleles) in the Genome Aggregation Database. The aspartate at codon 3064 is weakly conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.311). Due to limited information, the clinical significance of the p.Asp3064Asn variant is uncertain at this time. |
| Sharing Clinical Reports Project |
RCV000077462 | SCV000109260 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2012-03-20 | no assertion criteria provided | clinical testing | |
| Breast Cancer Information Core |
RCV000077462 | SCV000147562 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-05-29 | no assertion criteria provided | clinical testing | |
| Mayo Clinic Laboratories, |
RCV000590167 | SCV000778723 | uncertain significance | not provided | 2015-10-07 | no assertion criteria provided | clinical testing | |
| True Health Diagnostics | RCV000130150 | SCV000886677 | likely benign | Hereditary cancer-predisposing syndrome | 2018-08-07 | no assertion criteria provided | clinical testing |