ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.231T>G (p.Thr77=) (rs114446594)

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Total submissions: 17
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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) RCV000119247 SCV000321190 benign Breast-ovarian cancer, familial 2 2016-09-28 reviewed by expert panel curation Class 1 not pathogenic based on frequency >1% in an outbred sampleset. Frequency 0.0113 (African), derived from 1000 genomes (2013-05-02).
Invitae RCV000195302 SCV000071986 benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
Counsyl RCV000119247 SCV000154083 likely benign Breast-ovarian cancer, familial 2 2014-03-14 criteria provided, single submitter literature only
Ambry Genetics RCV000129199 SCV000183943 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing This alteration is classified as 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 RCV000176971 SCV000228765 benign not specified 2014-12-29 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000119247 SCV000267726 benign Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000195302 SCV000296852 likely benign Hereditary breast and ovarian cancer syndrome 2015-11-30 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000176971 SCV000538469 likely benign not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ClinVar: 5 B/LB; Silent (meets our criteria for LB)
Baylor Genetics RCV000466597 SCV000541058 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Institute for Biomarker Research,Medical Diagnostic Laboratories, L.L.C. RCV000195302 SCV000576432 likely benign Hereditary breast and ovarian cancer syndrome 2017-02-14 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000176971 SCV000602827 benign not specified 2016-11-17 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129199 SCV000683478 benign Hereditary cancer-predisposing syndrome 2015-03-10 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000176971 SCV000805671 benign not specified 2016-12-08 criteria provided, single submitter clinical testing
Mendelics RCV000195302 SCV000838724 benign Hereditary breast and ovarian cancer syndrome 2018-07-02 criteria provided, single submitter clinical testing
Mendelics RCV000119247 SCV001138949 benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353938 SCV000591665 benign Malignant tumor of breast no assertion criteria provided clinical testing The p.Thr77Thr variant has been identified in 22 out of 1134 proband chromosomes (frequency 0.019) in individuals with breast and ovarian cancer phenotype, and was not identified in 300 control chromosomes (Cherbal 2010, Hadjisawas 2004, Hadjisawas 2003, Fackenthal 2011, Baumbach-abstract). However, it is listed in dbSNP database (ID#: rs114446594) with an average heterozygosity of 0.005+/-0.051, therefore increasing the likelihood of this variant to be benign. This variant is not expected to have clinical significance because it does not alter an amino acid residue, and is not located near a splice junction. In the UMD database, this variant has been identified in 3 (out of 10) individuals with breast or ovarian cancers, where a second pathogenic BRCA1 or BRCA2 mutation was also detected, suggesting that this is a benign variant. In a recent study, partial exon 3 skipping was suggested to be associated with this variant, however this information is not very predictive of pathogenicity (Thery 2011). In summary, based on above information we would lean towards a more benign role for this variant, therefore this variant is classified as Benign.
Mayo Clinic Laboratories, Mayo Clinic RCV000656582 SCV000778633 likely benign not provided 2017-08-02 no assertion criteria provided clinical testing

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