ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.441A>G (p.Gln147=) (rs80358676)

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Total submissions: 8
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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) RCV000083105 SCV000578756 likely benign Breast-ovarian cancer, familial 2 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/).
Invitae RCV000044411 SCV000072424 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000160020 SCV000210239 likely benign not specified 2017-10-04 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 RCV000163773 SCV000214354 likely benign Hereditary cancer-predisposing syndrome 2014-10-06 criteria provided, single submitter clinical testing
Color RCV000163773 SCV000683620 likely benign Hereditary cancer-predisposing syndrome 2015-10-21 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000160020 SCV001363894 uncertain significance not specified 2019-05-22 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.441A>G alters a non-conserved nucleotide resulting in a synonymous change. Several computational tools predict a significant impact on normal splicing: Five predict the variant creates a 3 prime acceptor site. One publication reports experimental evidence that this variant affects mRNA splicing using a mini-gene assay (Fraile-Bethencourt_2019). However, this splicing effect has not been confirmed in patients. The variant allele was found at a frequency of 3.6e-05 in 250978 control chromosomes. To our knowledge, no occurrence of c.441A>G in individuals affected with Hereditary Breast and Ovarian Cancer has been reported. Co-occurrences with other pathogenic variant(s) have been reported (BRCA1 c.2389_2390delGA, p.Glu797Thrfs), providing supporting evidence for a benign role. 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 Likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
Sharing Clinical Reports Project (SCRP) RCV000083105 SCV000115179 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000083105 SCV000146868 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing

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