ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5552T>G (p.Ile1851Ser) (rs80358776)

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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) RCV000031553 SCV001161519 benign Breast-ovarian cancer, familial 2 2019-06-18 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 = 0.00059
Invitae RCV001081549 SCV000072692 benign Hereditary breast and ovarian cancer syndrome 2019-12-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV000131533 SCV000186527 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing
GeneDx RCV000044679 SCV000210614 likely benign not specified 2017-07-28 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.
Fulgent Genetics,Fulgent Genetics RCV000031553 SCV000575750 uncertain significance Breast-ovarian cancer, familial 2 2016-01-26 criteria provided, single submitter clinical testing
Color RCV000131533 SCV000683711 likely benign Hereditary cancer-predisposing syndrome 2015-04-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044679 SCV000918861 likely benign not specified 2018-01-25 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5552T>G (p.Ile1851Ser) variant involves the alteration of a non-conserved nucleotide. 3/5 in silico tools predict a benign outcome for this variant. This variant was found in 14/264030 control chromosomes at a frequency of 0.000053, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). This variant was identified in one affected individual who also tested positive for a known pathogenic mutation in BRCA2 (BIC database), and in two cancer-free individuals older than age 70 (FLOSSIES database), suggesting a non-pathogenic role. In addition, multiple reputable databases/diagnostic centers classified the variant of interest as "Likely Benign/Benign". Taken together, the variant was classified as Likely Benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000034447 SCV001148986 uncertain significance not provided 2019-02-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000044679 SCV001157757 uncertain significance not specified 2018-07-17 criteria provided, single submitter clinical testing The BRCA2 c.5552T>G; p.Ile1851Ser variant (rs80358776), to our knowledge, has not been described in the medical literature but contains an entry in ClinVar (Variation ID: 37972). It is observed in the European (Non-Finnish) population at an overall frequency of 0.01% (11/110504 alleles) in the Genome Aggregation Database. The isoleucine at codon 1851 is weakly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is tolerated. However, due to lack of clinical and functional data regarding this variant, its clinical significance cannot be determined with certainty.
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034447 SCV000043214 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Sharing Clinical Reports Project (SCRP) RCV000031553 SCV000054158 benign Breast-ovarian cancer, familial 2 2008-12-10 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031553 SCV000146632 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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