ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5170A>G (p.Ile1724Val) (rs35335654)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131376 SCV000186352 likely benign Hereditary cancer-predisposing syndrome 2017-12-27 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)
GeneDx RCV000160227 SCV000210611 likely benign not specified 2017-12-04 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.
Invitae RCV000587993 SCV000260001 likely benign not provided 2019-01-30 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000206856 SCV000494389 likely benign Hereditary breast and ovarian cancer syndrome 2015-08-06 criteria provided, single submitter clinical testing Variant summary: c.5170A>G affects a non-conserved nucleotide, resulting in amino acid change from Ile to Val. 4/4 in-silico tools predict benign outcome as well as MutationTaster predicts it to be a polymorphism. This variant was found in 9/118666 control chromosomes, predominantly in individuals of African descent at a frequency of 0.00082. This frequency is higher than maximal expected frequency of a pathogenic allele (0.0007503) in BRCA2 gene, suggesting this variant is an ethnic-specific rare polymorphism. The fact that this variant co-occurred with a truly deleterious mutation in BRCA1 gene, supports a "non-disease causing" nature of this variant. In addition, clinical laboratories classified this variant as likely benign/benign. Taken together, this variant was classified as Likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000160227 SCV000600628 likely benign not specified 2017-03-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587993 SCV000694834 likely benign not provided 2017-03-13 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5170A>G (p.Ile1724Val) variant involves the alteration of a non-conserved nucleotide, resulting in a missense substitution. The variant does not lie within a known functional domain and 4/4 in silico tools predict a benign outcome (SNPs&GO not captured due to low reliability index). This variant was found in the large control population database ExAC in 8/118592 control chromosomes and all 8 occurrences were observed in the African subpopulation, for a frequency of 0.000817 (8/9796). This frequency is greater than 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 African origin. Multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. In addition, the BIC database shows the variant as being detected in 3 individuals, 1 of which has a co-occuring pathogenic BRCA1 mutation (c.824_825ins10 in BRCA1 gene [#35027]), suggesting a benign nature for the variant of interest. To our knowledge, the variant of interest has not been reported in affected individuals via publications, nor evaluated for functional impact by in vivo/vitro studies. Taken together, the variant is classified as likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587993 SCV000887843 likely benign not provided 2018-05-02 criteria provided, single submitter clinical testing
Color RCV000131376 SCV000903441 benign Hereditary cancer-predisposing syndrome 2015-11-16 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000082938 SCV000115012 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000082938 SCV000146556 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing
3DMed Clinical Laboratory Inc RCV000677857 SCV000804018 likely benign Ovarian cancer 2018-01-02 no assertion criteria provided clinical testing

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