ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.9606G>A (p.Pro3202=) (rs755890067)

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Total submissions: 10
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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) RCV000495294 SCV000578579 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/).
Ambry Genetics RCV000164400 SCV000215036 likely benign Hereditary cancer-predisposing syndrome 2014-08-04 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 RCV001087565 SCV000560441 likely benign Hereditary breast and ovarian cancer syndrome 2020-09-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000460818 SCV000600870 likely benign not provided 2020-07-13 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000504386 SCV000695256 likely benign not specified 2019-08-08 criteria provided, single submitter clinical testing
Color Health, Inc RCV000164400 SCV000906706 likely benign Hereditary cancer-predisposing syndrome 2017-09-05 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001110896 SCV001268385 uncertain significance Fanconi anemia, complementation group D1 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000495294 SCV001268386 uncertain significance Breast-ovarian cancer, familial 2 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000460818 SCV001939399 benign not provided 2015-04-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000460818 SCV000592295 likely benign not provided no assertion criteria provided clinical testing The p.Pro3202Pro was identified in a cohort of Italian ovarian cancer patients, with frequency unspecified, as a polymorphism with no clinical significance (Minucci 2015). The variant was also identified in dbSNP (ID: rs755890067) “With Likely benign allele”, Clinvitae database (classification likely benign), the ClinVar database (classified as likely benign by Ambry Genetics and Invitae), UMD (13X with ”unclassified variant”), co-occurring with a pathogenic BRCA1 variant (c.4183C>T, p.Gln1395X); and in the Exome Aggregation Consortium (ExAC) database (released Jan 13, 2015) in 6 of 66734 chromosomes (frequency: 0.00008) from a population of European (Non-Finnish) individuals, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. It was not identified in East Asian, Other, African, Latino, South Asian, and European (Finnish) populations in EXAC. The p.Pro3202Pro 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, 4 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as likely benign.

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