ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3304A>T (p.Asn1102Tyr) (rs28897719)

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Total submissions: 12
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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) RCV000031414 SCV000244436 benign Breast-ovarian cancer, familial 2 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000083
Invitae RCV001079980 SCV000072188 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000590063 SCV000210588 likely benign not provided 2020-06-10 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24323938, 18724707, 17924331, 21990134, 24817641)
Ambry Genetics RCV000163002 SCV000213490 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing This alteration is classified as 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.
Counsyl RCV000031414 SCV000488937 benign Breast-ovarian cancer, familial 2 2016-07-26 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212227 SCV000600546 likely benign not specified 2017-06-24 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163002 SCV000683544 likely benign Hereditary cancer-predisposing syndrome 2017-04-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000212227 SCV000694689 benign not specified 2021-04-01 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.3304A>T (p.Asn1102Tyr) 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 2.6e-05 in 230504 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.3304A>T in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. At-least two co-occurrences with other pathogenic variant(s) have been observed at our laboratory (BRCA2 c.1929delG, p.Arg645fsX15; PALB2 c.1317delG, p.Phe440fs), providing supporting evidence for a benign role. Multifactorial probability models also support a neutral outcome (example, Lindor_2012, Easton_2007). Six clinical diagnostic laboratories and one expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as benign (n=2 to include the expert panel)/likely benign (n=5). Based on the evidence outlined above, the variant was classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590063 SCV000887786 likely benign not provided 2019-08-30 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001642306 SCV001854759 benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
Sharing Clinical Reports Project (SCRP) RCV000031414 SCV000054019 benign Breast-ovarian cancer, familial 2 2011-03-10 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031414 SCV000146211 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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