Total submissions: 21
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000077248 | SCV001161577 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2019-06-18 | reviewed by expert panel | curation | Variant allele has low bioinformatic likelihood to encode a missense alteration affecting protein function (Missense prior probability 0.02; http://priors.hci.utah.edu/PRIORS/), AND low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/), AND minor allele frequency 0.00415 (African), derived from gnomAD v2.1.1 non-cancer (2019-05-13). |
Invitae | RCV001079609 | SCV000071747 | benign | Hereditary breast ovarian cancer syndrome | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000131469 | SCV000186456 | likely benign | Hereditary cancer-predisposing syndrome | 2018-10-18 | 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. |
Gene |
RCV000589778 | SCV000210554 | likely benign | not provided | 2021-05-24 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 25348012, 20104584, 26315209, 24504028, 23555315, 18284688, 21520273) |
Eurofins Ntd Llc |
RCV000173638 | SCV000224769 | likely benign | not specified | 2015-01-08 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589778 | SCV000694503 | likely benign | not provided | 2016-04-11 | criteria provided, single submitter | clinical testing | Variant summary: The c.1040A>G variant affects a non-conserved nucleotide, resulting in amino acid change from Gln to Arg. 4/5 in-silico tools predict this variant to be benign. This variant is found in 47/120376 control chromosomes at a frequency of 0.0003904, however is present at 10-fold higher frequency in the African population (0.004533 in ExAC), which exceeds the maximum expected allele frequency for a pathogenic variant in BRCA2 (0.0007503). This suggests that this variant is a benign polymorphism in populations of African origin. This variant has been reported in BrC or OvC patients without evidence for causality. Multiple clinical laboratories classified this variant as benign/likely benign. Taken together, this variant is classified as Likely Benign until additional information becomes available. |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000077248 | SCV000744400 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2015-09-21 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000589778 | SCV000805645 | likely benign | not provided | 2017-05-05 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000589778 | SCV000883473 | likely benign | not provided | 2022-05-06 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000589778 | SCV000887744 | benign | not provided | 2023-05-03 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000131469 | SCV000902747 | benign | Hereditary cancer-predisposing syndrome | 2016-01-05 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000173638 | SCV002065673 | uncertain significance | not specified | 2018-09-12 | criteria provided, single submitter | clinical testing | |
Genetics Program, |
RCV001079609 | SCV002515246 | likely benign | Hereditary breast ovarian cancer syndrome | 2021-11-01 | criteria provided, single submitter | research | |
Sema4, |
RCV000131469 | SCV002533202 | benign | Hereditary cancer-predisposing syndrome | 2020-12-02 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000173638 | SCV002550271 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Sharing Clinical Reports Project |
RCV000077248 | SCV000109045 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2008-05-22 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000077248 | SCV000145810 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2004-02-20 | no assertion criteria provided | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001353763 | SCV000591726 | likely benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The BRCA2 p.Gln347Arg variant was identified in dbSNP (ID: rs55800493) “With likely benign, other allele”, with a minor allele frequency of 0.0024 (1000 Genomes Project), Clinvitae database, the ClinVar database (classified as a “likely benign” by Invitae, Ambry Genetics, GeneDx, Emory Genetics Laboratory and Sharing Clinical Reports Project), the BIC database (9X with unknown clinical importance), and UMD (2X as an unknown variant). This variant was also identified in the Exome Variant Server project in 17 of 4400 European American alleles, and the Exome Aggregation Consortium (ExAC) database (released Jan 13, 2015) in 45 of 9928 chromosomes (frequency: 0.0045) from a population of African individuals. The variant was also found at low frequencies in Latino (8.66E-05) and European (Non-Finnish) individuals (1.51E-05), although this low number of observations and low frequency is not substantive enough to determine the prevalence of the variant in the general population and its relationship to disease. The p.Gln347 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein. However, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as likely benign. | |
Genome Diagnostics Laboratory, |
RCV000077248 | SCV000745675 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2017-05-21 | no assertion criteria provided | clinical testing | |
Clinical Genetics Laboratory, |
RCV000173638 | SCV001905797 | benign | not specified | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000173638 | SCV001978080 | benign | not specified | no assertion criteria provided | clinical testing |