ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6143A>T (p.Asn2048Ile) (rs80358853)

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Total submissions: 13
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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) RCV000113536 SCV000244463 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 = 0.0000319
GeneDx RCV000589722 SCV000210624 likely benign not provided 2020-12-16 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24323938, 21990134, 17924331)
Ambry Genetics RCV000163009 SCV000213497 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.
Invitae RCV001081075 SCV000260760 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-03 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000160232 SCV000602831 likely benign not specified 2016-11-22 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000160232 SCV000694944 benign not specified 2021-04-02 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.6143A>T (p.Asn2048Ile) 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 8e-06 in 250954 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.6143A>T in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Multifactorial probability based models have predicted a neutral outcome for this variant (example, Easton_2007, Lindor_2012). Multiple co-occurrences with other pathogenic variant(s) have been reported in the BIC database (BRCA2 c.6373_6374insA, p.Thr2125?fs; BRCA1 c.5503C>T, p.Arg1835X; BRCA2 c.7758G>A, p.Trp2586Ter; BRCA2 c.7758G>A, p.Trp2586Ter), providing supporting evidence for a benign role. Six clinical diagnostic laboratories and an expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and a majority consensus of likely benign (n=4)/benign(n=2). Based on the evidence outlined above, the variant was classified as benign.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000589722 SCV000859742 uncertain significance not provided 2018-03-08 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000589722 SCV000887867 likely benign not provided 2019-05-15 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163009 SCV000910769 benign Hereditary cancer-predisposing syndrome 2016-02-22 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001642405 SCV001854868 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
Breast Cancer Information Core (BIC) (BRCA2) RCV000113536 SCV000146778 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000160232 SCV001741560 benign not specified no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000160232 SCV001906180 benign not specified no assertion criteria provided clinical testing

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