ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3417G>A (p.Lys1139=) (rs145625991)

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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) RCV000495720 SCV000579107 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 RCV000755222 SCV000166165 benign not provided 2019-03-03 criteria provided, single submitter clinical testing
GeneDx RCV000123962 SCV000167354 benign not specified 2014-02-07 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 RCV000162706 SCV000213166 likely benign Hereditary cancer-predisposing syndrome 2014-07-14 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000123962 SCV000591859 likely benign not specified 2015-06-30 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755222 SCV000602810 benign not provided 2018-01-16 criteria provided, single submitter clinical testing
Color RCV000162706 SCV000683554 likely benign Hereditary cancer-predisposing syndrome 2015-10-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000123962 SCV000916995 likely benign not specified 2017-12-28 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.3417G>A (p.Lys1139Lys) 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. 3/5 in silico tools predict that this variant may affect a normal splicing. ESE finder predicts that this variant may affect ESE site of SF2/ASF. However, these predictions have yet to be confirmed by functional studies. This variant was found in 36/245756 control chromosomes, predominantly observed in the Ashkenazi Jewish subpopulation at a frequency of 0.003556 (35/9842). This frequency is about 5 times 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 Ashkenazi Jewish origin. The variant has been reported in one breast cancer case, however, no co-segregation and/or co-occurrence information was provided (Borg 2010). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as likely benign.

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