ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.765G>A (p.Glu255=) (rs62625299)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000123285 SCV000166592 benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
GeneDx RCV000173830 SCV000167235 benign not specified 2014-01-29 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.
Ambry Genetics RCV000163053 SCV000213545 likely benign Hereditary cancer-predisposing syndrome 2014-09-18 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000173830 SCV000224986 likely benign not specified 2014-10-07 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000211047 SCV000267687 benign Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
Baylor Genetics RCV000469425 SCV000540964 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282996 SCV000602728 likely benign none provided 2019-12-23 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163053 SCV000683355 likely benign Hereditary cancer-predisposing syndrome 2015-10-09 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001354387 SCV001548993 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA1 p.Glu255= variant was identified in 2 of 1230 proband chromosomes (frequency: 0.0016) from individuals or families with breast or ovarian cancer (Fackenthal 2012, Trujillano 2015). The variant was also identified in dbSNP (ID: rs62625299) as "With other allele ", ClinVar (classified as benign by Invitae, GeneDx, and two other clinical laboratories; classified as likely benign by Ambry Genetics, Color Genomics, ARUP and one otherclinical laboratory), LOVD 3.0 (8x), and in UMD-LSDB (6x as unclassified variant). The variant was not identified in COGR, Cosmic, BIC Database, ARUP Laboratories, or Zhejiang University, databases. The variant was identified in control databases in 105 of 275132 chromosomes at a frequency of 0.0004 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 97 of 23988 chromosomes (freq: 0.004), Other in 1 of 6418 chromosomes (freq: 0.000216), Latino in 6 of 34064 chromosomes (freq: 0.000218), and European in 1 of 125766 chromosomes (freq: 0.000008), but not in the Ashkenazi Jewish, East Asian, Finnish, and or South Asian populations. The p.Glu255= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, 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 although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.