ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.522A>G (p.Gln174=) (rs765432756)

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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) RCV000211001 SCV000578177 likely benign Breast-ovarian cancer, familial 1 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/).
Ambry Genetics RCV000163148 SCV000213665 likely benign Hereditary cancer-predisposing syndrome 2014-07-23 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000587830 SCV000232251 uncertain significance not provided 2014-08-18 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000211001 SCV000267683 likely benign Breast-ovarian cancer, familial 1 2016-04-21 criteria provided, single submitter clinical testing
GeneDx RCV000179931 SCV000517463 likely benign not specified 2017-02-24 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.
Department of Pathology and Molecular Medicine,Queen's University RCV000179931 SCV000588029 likely benign not specified 2017-04-20 criteria provided, single submitter clinical testing
Invitae RCV001082885 SCV000636021 likely benign Hereditary breast and ovarian cancer syndrome 2020-11-06 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163148 SCV000683273 likely benign Hereditary cancer-predisposing syndrome 2017-04-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000179931 SCV000699225 likely benign not specified 2019-08-21 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587830 SCV001470181 likely benign not provided 2020-03-17 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356661 SCV001551891 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA1 p.Gln174= variant was not identified in the literature nor was it identified in the LOVD 3.0, BIC Database, or ARUP Laboratories database. The variant was identified in dbSNP (ID: rs765432756) “With other allele”, ClinVar (classified likely benign by ENIGMA, Invitae, Color, Ambry Genetics, GeneDx and Michigan Medical Genetics Laboratories; and as uncertain significance by two submitters), and UMD-LSDB (classified as 3-UV). The variant was identified in control databases in 5 of 277216 chromosomes at a frequency of 0.00002 (Genome Aggregation Database Feb 27, 2017), observed in the European Non-Finnish population in 5 of 126696 chromosomes (freq: 0.00004), while it was not observed in the African, Other, Latino, Ashkenazi Jewish, East Asian, European Finnish, or South Asian populations. The p.Gln174= 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) 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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