ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3299A>T (p.Asn1100Ile) (rs80358575)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000656794 SCV000072186 likely benign not provided 2019-01-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129737 SCV000184543 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-14 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other data supporting benign classification,Insufficient or conflicting evidence
GeneDx RCV000656794 SCV000210528 uncertain significance not provided 2018-05-16 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.3299A>T at the cDNA level, p.Asn1100Ile (N1100I) at the protein level, and results in the change of an Asparagine to an Isoleucine (AAC>ATC). Using alternate nomenclature, this variant would be defined as BRCA2 3527A>T. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Asn1100Ile was not observed at a significant allele frequency in large population cohorts (Lek 2016). BRCA2 Asn1100Ile is located within the RAD51 Binding Domain (Roy 2012). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BRCA2 Asn1100Ile is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Counsyl RCV000031413 SCV000488753 uncertain significance Breast-ovarian cancer, familial 2 2016-06-07 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000044173 SCV000600544 uncertain significance not specified 2017-04-28 criteria provided, single submitter clinical testing
Color RCV000129737 SCV000906673 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-03 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044173 SCV000918991 uncertain significance not specified 2018-08-08 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3299A>T (p.Asn1100Ile) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.8e-05 in 225178 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3299A>T in individuals affected with Hereditary Breast and Ovarian Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014: four classified the variant as uncertain significance and one classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Mendelics RCV000031413 SCV001139060 uncertain significance Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031413 SCV000054018 likely benign Breast-ovarian cancer, familial 2 2011-02-03 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031413 SCV000146209 uncertain significance Breast-ovarian cancer, familial 2 2003-12-23 no assertion criteria provided clinical testing

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