ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2145A>G (p.Gly715=) (rs112566179)

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Total submissions: 9
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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) RCV000495123 SCV000578023 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 0.0014 (African), derived from ExAC (2014-12-17).
GeneDx RCV000160214 SCV000210575 benign not specified 2014-06-22 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 RCV000162803 SCV000213284 likely benign Hereditary cancer-predisposing syndrome 2014-07-10 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001079130 SCV000252606 benign Hereditary breast and ovarian cancer syndrome 2020-11-24 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160214 SCV000600502 likely benign not specified 2017-04-27 criteria provided, single submitter clinical testing
Color Health, Inc RCV000162803 SCV000683470 benign Hereditary cancer-predisposing syndrome 2015-09-30 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000160214 SCV000861269 likely benign not specified 2018-05-29 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759589 SCV000889005 benign not provided 2018-06-13 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000495123 SCV001549664 likely benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing The BRCA2 p.Gly715= variant was identified in 1 of 820 proband chromosomes (frequency: 0.001) from individuals or families with breast cancer (Fackenthal 2012). The variant was also identified in dbSNP (ID: rs112566179) as "With other allele", ClinVar (classified as benign by Invitae, GeneDx, Color and ENIGMA; as likely benign by three submitters), LOVD 3.0 (3x), and in UMD-LSDB (4x as unclassified variant). The variant was identified in UMD-LSDB with a co-occurring pathogenic BRCA2 variant (c.6159delT, p.Ala2054Leufs*16), increasing the likelihood that the p.Gly715= variant does not have clinical significance. The variant was identified in control databases in 43 of 277062 chromosomes at a frequency of 0.0002 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 42 of 24028 chromosomes (freq: 0.002) and Latino in 1 of 34366 chromosomes (freq: 0.00003), while the variant was not observed in the Other, European, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Gly715= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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