ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3495T>C (p.His1165=) (rs776655838)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167473 SCV000218329 likely benign Hereditary cancer-predisposing syndrome 2015-01-04 criteria provided, single submitter clinical testing
Color RCV000167473 SCV000683561 likely benign Hereditary cancer-predisposing syndrome 2017-02-10 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000495612 SCV000578013 benign Breast-ovarian cancer, familial 2 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 0.0011 (Admixed American/Latino), derived from ExAC (2014-12-17).
GeneDx RCV000604215 SCV000729262 likely benign not specified 2018-02-21 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.
Illumina Clinical Services Laboratory,Illumina RCV000343589 SCV000383679 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000395567 SCV000383680 uncertain significance Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588878 SCV000694700 likely benign not provided 2017-08-21 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.3495T>C (p.His1165His) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may multiple affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 13/121250 control chromosomes, predominantly observed in the Latino subpopulation at a frequency of 0.001124 (13/11562). This frequency is higher than the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/other clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely benign.
Invitae RCV000343589 SCV000560446 benign Hereditary breast and ovarian cancer syndrome 2017-12-28 criteria provided, single submitter clinical testing

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