ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7317A>G (p.Gly2439=) (rs587780660)

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Total submissions: 10
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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) RCV000495379 SCV000579037 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 RCV000122927 SCV000166185 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-18 criteria provided, single submitter clinical testing
GeneDx RCV000160241 SCV000210647 benign not specified 2014-06-11 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 RCV000163513 SCV000214071 likely benign Hereditary cancer-predisposing syndrome 2015-08-16 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000122927 SCV000494402 uncertain significance Hereditary breast and ovarian cancer syndrome 2016-06-27 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7317A>G (p.Gly2439Gly) 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 along with 5/5 splice prediction tools predicting the variant not to have an impact on normal splicing. This variant was found in 4/121258 control chromosomes at a frequency of 0.000033, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant was reported in three sporadic breast cancer cases however without strong evidence for pathogenicity such as co-occurrence and co-segregation (de Juan Jimenez_2012). The variant has been reported by clinical diagnostic laboratories with a classification of "likely benign/benign" via ClinVar. Therefore, until additional information becomes available; this variant has been classified as VUS-possibly benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160241 SCV000600742 likely benign not specified 2016-12-16 criteria provided, single submitter clinical testing
Color RCV000163513 SCV000683864 likely benign Hereditary cancer-predisposing syndrome 2015-12-29 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589434 SCV000695055 uncertain significance not provided 2017-04-07 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7317A>G (p.Gly2439Gly) 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 and ESE finder predicts that this variant does not significantly impact ESE sites at the locus. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC at a frequency of 0.000033 (4/121258 control chromosomes), which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant was reported in three sporadic breast cancer cases, but without strong evidence for pathogenicity such as co-occurrence and co-segregation (de Juan Jimenez_BRCA1&2_Fam Cancer_2012). In addition, multiple clinical diagnostic laboratories/ databases classified this variant as likely benign/ benign/VUS, all without evidence for indpendent evaluation. Taken together, this variant is classified as VUS-possibly benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000589434 SCV000885110 benign not provided 2017-07-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589434 SCV000887912 likely benign not provided 2018-06-01 criteria provided, single submitter clinical testing

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