ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.795T>C (p.Ser265=) (rs201441987)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000112789 SCV000577994 benign Breast-ovarian cancer, familial 1 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/) and frequency 0.0031 (East Asian), derived from ExAC (2014-12-17).
Invitae RCV001082438 SCV000077153 benign Hereditary breast and ovarian cancer syndrome 2020-12-06 criteria provided, single submitter clinical testing
Ambry Genetics RCV000163599 SCV000214162 likely benign Hereditary cancer-predisposing syndrome 2014-09-30 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.
Cancer Genetics and Genomics Laboratory,British Columbia Cancer Agency RCV000496381 SCV000586871 likely benign not specified 2017-04-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587508 SCV000600437 benign not provided 2018-10-16 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163599 SCV000683358 likely benign Hereditary cancer-predisposing syndrome 2016-02-17 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587508 SCV000699302 likely benign not provided 2017-02-21 criteria provided, single submitter clinical testing Variant summary: The BRCA1 795T>C (p.Ser265Ser) variant causes a synonymous change involving the alteration of a conserved nucleotide, which 5/5 splice prediction tools predict no significant impact on normal splicing. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 27/121032 (1/4482), predominantly in the East Asian cohort, 27/8652 (1/320), which does exceed the estimated maximal expected allele frequency for a pathogenic BRCA1 variant of 1/1000. Therefore, suggesting the variant is a benign polymorphism found in population(s) of East Asian origin. A functional study, Raponi_2012 reports that the variant could influence the use of an alternative splice site reducing the D(11a) isoform, however, this functional experiment alone is not sufficient evidence to suggest pathogenicity. In addition, Thirthagiri_2008 and Judkins_2005, along with multiple clinical diagnostic laboratories classify the variant as "likely benign/benign/polymorphism." Taken together, this variant is classified as a "likely benign."
Counsyl RCV000112789 SCV000786089 likely benign Breast-ovarian cancer, familial 1 2018-02-20 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000112789 SCV000145685 uncertain significance Breast-ovarian cancer, familial 1 2010-09-18 no assertion criteria provided clinical testing

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