ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.3672C>T (p.Gly1224=) (rs587780650)

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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) RCV000495475 SCV000578734 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; http://priors.hci.utah.edu/PRIORS/).
Invitae RCV001085375 SCV000166166 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000164840 SCV000215523 likely benign Hereditary cancer-predisposing syndrome 2014-06-20 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507541 SCV000600559 likely benign not specified 2017-03-28 criteria provided, single submitter clinical testing
Color Health, Inc RCV000164840 SCV000683570 likely benign Hereditary cancer-predisposing syndrome 2015-07-24 criteria provided, single submitter clinical testing
Counsyl RCV000495475 SCV000785874 likely benign Breast-ovarian cancer, familial 2 2017-12-21 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000755870 SCV000883500 likely benign not provided 2018-02-01 criteria provided, single submitter clinical testing The BRCA2 c.3672C>T; p.Gly1224Gly variant (rs587780650), to our knowledge, is not reported in the medical literature but is reported as likely benign by multiple labs in ClinVar (Variation ID: 135797). Additionally, another variant at this nucleotide position (c.3672C>G; p.Gly1224Gly) has also been reported as likely benign to ClinVar (Variation ID: 481605). The c.3672C>T variant is found in the general population at an overall frequency of 0.003% (1/30934 alleles) in the Genome Aggregation Database. This is a synonymous change, the nucleotide is weakly conserved, and computational algorithms (SpliceSiteFinder-like, MaxEntScan, NNSplice, GeneSplicer, Human Splicing Finder) do not predict that this variant impacts splicing. Based on the above information, this variant is considered likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000755870 SCV000889024 likely benign not provided 2020-05-29 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770720 SCV000902199 likely benign Breast and/or ovarian cancer 2017-08-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000507541 SCV000918880 likely benign not specified 2020-11-12 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000755870 SCV001551167 uncertain significance not provided no assertion criteria provided clinical testing The BRCA2 p.Gly1224= variant was not identified in the literature nor was it identified in the COGR, COSMIC, MutDB, UMD, LOVD 3.0, BIC, ARUP Laboratories BRCA Mutations Database or Zhejiang University database. The variant was identified in dbSNP (ID: rs587780650) as "With Likely benign allele", and in Clinvar database (classified as likely benign by Invitae, Ambry Genetics and 4 other submitters). The variant was identified in control databases in 1 of 30934 chromosomes at a frequency of 0.000032 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the “Other” population in 1 of 978 chromosomes (freq: 0.001); it was not observed in the African, Latino, European, Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The p.Gly1224= 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 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) 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 a variant of uncertain significance.

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