ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5635G>A (p.Glu1879Lys) (rs55996097)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000755862 SCV000883488 likely benign not provided 2017-09-06 criteria provided, single submitter clinical testing The p.Glu1879Lys variant has been reported in individuals with breast and/or ovarian cancer; however, inheritance and specific clinical information were not reported (Borg 2010, Pennington 2012, and Thirthagiri 2008). The p.Glu1879Lys variant is listed in the Genome Aggregation Database (gnomAD) browser with an allele frequency of 0.023% in the South Asian population (identified in 7 out of 29,948 chromosomes; 1 homozygote), and is classified as likely benign/benign in ClinVar (Variant ID: 51895). The glutamic acid at codon 1,879 is moderately conserved considering 12 species (Alamut software v2.9.0), and it is a lysine in dogs, suggesting that this change may be evolutionary tolerated. Computational analyses predict that this variant does not affect the BRCA2 protein structure/function (GV/GD: C0, SIFT: tolerated, PolyPhen2: benign, MutationTaster: polymorphism). Based on the available evidence, the p.Glu1879Lys variant is classified as likely benign.
Ambry Genetics RCV000129072 SCV000183775 likely benign Hereditary cancer-predisposing syndrome 2017-12-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,In silico models in agreement (benign)
Breast Cancer Information Core (BIC) (BRCA2) RCV000077357 SCV000146649 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000129072 SCV000902758 benign Hereditary cancer-predisposing syndrome 2016-09-08 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000077357 SCV000744471 likely benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000077357 SCV000733268 likely benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
GeneDx RCV000168580 SCV000210616 likely benign not specified 2017-11-28 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.
Illumina Clinical Services Laboratory,Illumina RCV000336386 SCV000383719 likely benign Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000167807 SCV000383720 likely benign Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000168580 SCV000694886 likely benign not specified 2017-12-22 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5635G>A (p.Glu1879Lys) variant involves the alteration of a non-conserved nucleotide. The variant is located outside of any known functional domain or repeat and 4/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 35/274724 control chromosomes at a frequency of 0.0001274 (including 1 homozygous occurrence). Although this frequency does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503), the variant may represent a functional polymorphism. The variant of interest has been observed in multiple affected individuals via publications with limited addition information such as co-occurrence and/or co-segregation information. However, a reputable database, UMD cites the variant co-occurring with another pathogenic BRCA2 variant, c.8463dup (p.Ille2822TyrfsX23) as well as BIC citing the variant in an individual carrying a pathogenic BRCA1 variant (BRCA1 c.5263_5264insC, p.Ser1755?fs) in addition to a homozygous occurrence in presumably unaffected individual from gnomAD dataset. In addition, multiple reputable diagnostic laboratories have classified the variant as "likely benign/benign." Taken together, by applying ACMG rules (BS2, BP4, BP5 and BP6) this variant is classified as Likely Benign variant.
Invitae RCV000167807 SCV000072715 benign Hereditary breast and ovarian cancer syndrome 2017-12-23 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000077357 SCV000296630 uncertain significance Breast-ovarian cancer, familial 2 2016-05-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000755862 SCV000887853 likely benign not provided 2017-12-09 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000077357 SCV000109154 benign Breast-ovarian cancer, familial 2 2009-08-24 no assertion criteria provided clinical testing

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