ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.1944A>G (p.Glu648=) (rs876660781)

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Total submissions: 6
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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) RCV000494919 SCV000578246 likely benign Breast-ovarian cancer, familial 1 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Ambry Genetics RCV000213340 SCV000278470 likely benign Hereditary cancer-predisposing syndrome 2015-09-19 criteria provided, single submitter clinical testing
GeneDx RCV000439810 SCV000518071 likely benign not specified 2016-07-18 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.
Invitae RCV000535108 SCV000635820 likely benign Hereditary breast and ovarian cancer syndrome 2017-07-24 criteria provided, single submitter clinical testing
Color RCV000213340 SCV000904625 likely benign Hereditary cancer-predisposing syndrome 2017-11-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000439810 SCV000918791 uncertain significance not specified 2018-11-01 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1944A>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 245676 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1944A>G in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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