ClinVar Miner

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

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Total submissions: 10
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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 RCV000160232 SCV000210624 likely benign not specified 2017-10-27 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.
Ambry Genetics RCV000163009 SCV000213497 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
Invitae RCV001081075 SCV000260760 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 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
Integrated Genetics/Laboratory Corporation of America RCV000589722 SCV000694944 likely benign not provided 2016-04-01 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.6143A>T variant affects a non-conserved nucleotide, resulting in an amino acid change from a medium size and polar Asparagine (N) to a medium size and hydrophobic Isoleucine (I). 4/5 in-silico tools predict this variant to be damaging; however they are not definite. This variant was not found in approximately 120890 control chromosomes from the broad and large populations of ExAC; however it could still be a rare polymorphism. In BIC this variant has been reported to co-occur with pathogenic BRCA1/2 variants in three individuals undergoing BRCA1/2 screening, namely BRCA2 c.7758G>A (p.Trp2586Ter), BRCA2 c.6373_6374insA (p.Thr2125fs), and BRCA1 c.5503C>T (p.Arg1835Ter), suggesting that this variant is unlikely to be pathogenic. Multifactorial probability models also indicate that this variant is neutral (Easton_2007 and Lindor_2012). In addition, multiple clinical laboratories/reputable databases have classified this variant as benign/likely benign. Taken together, the variant has been classified as likely benign until additional information becomes available (i.e. functional studies and/or co-segregation data).
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 RCV000163009 SCV000910769 benign Hereditary cancer-predisposing syndrome 2016-02-22 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113536 SCV000146778 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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