ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2347A>G (p.Ile783Val) (rs80356948)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130405 SCV000185266 benign Hereditary cancer-predisposing syndrome 2015-08-29 criteria provided, single submitter clinical testing This alteration is classified as 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.
GeneDx RCV000254637 SCV000209936 likely benign not specified 2018-01-18 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000083181 SCV000296304 uncertain significance Breast-ovarian cancer, familial 1 2016-05-18 criteria provided, single submitter clinical testing
Counsyl RCV000083181 SCV000488046 uncertain significance Breast-ovarian cancer, familial 1 2015-12-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590349 SCV000698943 likely benign not provided 2016-08-11 criteria provided, single submitter clinical testing Variant summary: The c.2347A>G (p.Ile783Val) in BRCA1 gene is a missense change that involves a non-conserved nucleotide and 5/5 in silico tools predict benign outcome. The variant of interest is located outside of any known functional domain. The variant is present in the control population dataset of ExAC at an overall frequency 0.0001 (10/12134 chrs tested) exclusively in individuals of East Asian ancestry (0.0012; 10/8652 chrs tested). The latter frequency exceeds the estimated maximum allele frequency for a pathogenic allele in this gene (0.001). The variant was absent in a cohort of 645 Chinese BrC cases but was found in two Chinese subjects one of whom had a benign breast disease. The variant has been reported as Benign/Likely Benign by several reputable databases/clinical laboratories. Population data suggest that the variant may be an ethnic-specific benign rare polymorphism. Taking together, the variant was classified as Likely Benign.
Color Health, Inc RCV000130405 SCV000903502 benign Hereditary cancer-predisposing syndrome 2016-09-23 criteria provided, single submitter clinical testing
Invitae RCV001417426 SCV001619627 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000083181 SCV000115255 benign Breast-ovarian cancer, familial 1 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083181 SCV000144386 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353824 SCV000591381 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA1 p.Ile783Val variant was identified in at least 2 of 11262 probands referred for BRCA1/2 testing due to a personal history of early onset breast or ovarian cancer, and/or a family history of breast and/or ovarian cancer (Kurian 2008, Judkins 2005); however control chromosomes from healthy individuals were not evaluated in these studies. It is listed in the dbSNP database (rs80356948) but no frequency information was provided, thus the prevalence of this variant in the general population could not be determined. 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 p.Ile783 residue is not conserved in mammals and the variant amino acid valine (Val) is present in mouse, increasing the likelihood that this variant does not have clinical significance. In addition, the variant was classified as benign by the Sharing Clinical Reports Project (SCRP) (submitted within the ClinVar database and derived from Myriad reports). In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.

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