ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.7563C>A (p.Ile2521=) (rs786204282)

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Total submissions: 6
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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) RCV000495321 SCV000578685 likely benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02;
Invitae RCV000550510 SCV000635584 likely benign Hereditary breast and ovarian cancer syndrome 2020-04-10 criteria provided, single submitter clinical testing
GeneDx RCV000168604 SCV000732610 likely benign not specified 2017-06-07 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 RCV001026572 SCV001188979 likely benign Hereditary cancer-predisposing syndrome 2018-08-31 criteria provided, single submitter clinical testing Synonymous alterations with insufficient evidence to classify as benign
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001284441 SCV001470242 likely benign not provided 2019-12-05 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000495321 SCV001552588 uncertain significance Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing The BRCA2 p.Ile2521= variant was not identified in the literature nor was it identified in the Cosmic, LOVD 3.0, UMD-LSDB, BIC Database, ARUP Laboratories, or Zhejiang University databases. The variant was also identified in dbSNP (ID: rs786204282) as "With other allele", ClinVar (classified as likely benign by Invitae, GeneDx, and ENIGMA; and as uncertain significance by COGR), and in GeneInsight-COGR database. The variant was identified in control databases in 1 of 245904 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the East Asian population in 1 of 17240 chromosomes (freq: 0.00006), while the variant was not observed in the African, Other, Latino, European, Ashkenazi Jewish, Finnish, or South Asian populations. The p.Ile2521= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as uncertain significance.

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