ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.7712A>G (p.Glu2571Gly) (rs55689095)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000130819 SCV000185715 uncertain significance Hereditary cancer-predisposing syndrome 2017-11-01 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000113807 SCV000147165 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
Color RCV000130819 SCV000683901 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-14 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000045293 SCV000592137 uncertain significance not specified 2014-10-20 criteria provided, single submitter clinical testing
GeneDx RCV000590609 SCV000210443 uncertain significance not provided 2017-10-23 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.7712A>G at the cDNA level, p.Glu2571Gly (E2571G) at the protein level, and results in the change of a Glutamic Acid to a Glycine (GAA>GGA). Using alternate nomenclature, this variant would be defined as BRCA2 7940A>G. BRCA2 Glu2571Gly has been observed in at least two women with pre-menopausal and/or triple negative breast cancer (Haffty 2009, Francies 2015). BRCA2 Glu2571Gly was observed at an allele frequency of 0.05% (13/24,030) in individuals of African ancestry in large population cohorts (Lek 2016). Since Glutamic Acid and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Glu2571Gly occurs at a position where amino acids with properties similar to Glutamic Acid are tolerated across species and is located in the DNA binding domain (Yang 2002). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BRCA2 Glu2571Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000590609 SCV000695096 uncertain significance not provided 2017-04-24 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.7712A>G (p.Glu2571Gly) variant involves the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. This variant was found in 5/121342 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.000482 (5/10382). The variant is also present in a control population dataset of gnomAD at a frequency of 0.00005 (15/277138 chrs), mainly in individuals of African origin: 0.00054 (13/24030 chrs). Although, these frequencies do not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503), the prevalence of the variant in African sub-cohorts suggests that the variant of interest may be an ethnic-specific functional polymorphism. The variant has been reported in affected individuals of African origin in the literature, without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance, including one report of co-occurrence with a pathogenic BRCA1 variant, suggesting the variant of interest is not the primary cause of disease in that patient. Taken together, this variant is classified as VUS-Possibly Benign.
Invitae RCV000195380 SCV000073306 likely benign Hereditary breast and ovarian cancer syndrome 2017-12-05 criteria provided, single submitter clinical testing
Mendelics RCV000195380 SCV000838860 uncertain significance Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000045293 SCV000600766 uncertain significance not specified 2017-01-13 criteria provided, single submitter clinical testing

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