ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1167G>A (p.Pro389=) (rs148607710)

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Total submissions: 11
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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) RCV000494918 SCV000578830 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;
Ambry Genetics RCV000163590 SCV000214150 likely benign Hereditary cancer-predisposing syndrome 2014-09-04 criteria provided, single submitter clinical testing This alteration is classified as likely 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 RCV001086938 SCV000260877 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-20 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000590259 SCV000333318 uncertain significance not provided 2015-07-29 criteria provided, single submitter clinical testing
GeneDx RCV000302173 SCV000512337 benign not specified 2015-08-27 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000302173 SCV000600471 likely benign not specified 2017-03-31 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163590 SCV000688697 benign Hereditary cancer-predisposing syndrome 2016-05-19 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000302173 SCV000694515 likely benign not specified 2020-11-24 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000590259 SCV000885114 likely benign not provided 2017-09-19 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000590259 SCV000887750 benign not provided 2018-05-08 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356802 SCV001552067 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Pro389= variant was identified in 6 of 7082 proband chromosomes (frequency: 0.00085) from individuals or families with breast cancer and in 3 of 334 control chromosomes (frequency: 0.009) (Borg_2010, Ermolenko_2015, Kim_2006, Stegel_2011). The variant was also identified in dbSNP (ID: rs148607710) as “With other allele”, ClinVar (as likely benign reviewed by expert panel), Clinvitae (5x), COGR (as likely benign by COGR consensus), LOVD 3.0 (2x as uncertain significance), UMD-LSDB (5x as uncertain significance, co-occuring with a pathogenic BRCA1 variant p.Asn1355LysfsX10). The variant was not identified in Cosmic, MutDB, BIC Database, ARUP Laboratories, or Zhejiang Colon Cancer Database. The variant was identified in control databases in 18 of 277030 chromosomes at a frequency of 0.000065 (Genome Aggregation Database Feb 27, 2017). It was observed in the following populations: African in 1 of 24020 chromosomes (freq: 0.000042), Latino in 1 of 34398 chromosomes (freq: 0.000029), European (Non-Finnish) in 13 of 126618 chromosomes (freq: 0.000103), East Asian in 2 of 18866 chromosomes (freq: 0.000106), and South Asian in 1 of 30738 chromosomes (freq: 0.000033); but not observed in the Other, Ashkenazi Jewish, or European (Finnish) populations. The p.Pro389= 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. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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