ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.1166C>A (p.Pro389Gln) (rs397507263)

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Total submissions: 13
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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) RCV000082883 SCV001161604 benign Breast-ovarian cancer, familial 2 2019-06-18 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000287
Ambry Genetics RCV000129740 SCV000184546 likely benign Hereditary cancer-predisposing syndrome 2018-09-18 criteria provided, single submitter clinical testing Other strong data supporting benign classification;in silico models in agreement (benign)
Invitae RCV000197010 SCV000252603 benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000294429 SCV000383629 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 RCV000082883 SCV000383630 likely benign 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx RCV000436893 SCV000515841 likely benign not specified 2017-06-02 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 Laboratory Medicine,Sinai Health System RCV000436893 SCV000591731 likely benign not specified 2015-03-18 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000436893 SCV000600469 likely benign not specified 2017-05-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587492 SCV000694513 benign not provided 2016-06-22 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.1166C>A (p.Pro389Gln) variant involves the alteration of a non-conserved nucleotide. The variant is located outside of any known functional domain and 3/4 in silico tools predict a benign outcome (SNPs&GO not captured due to low reliability index). This variant was found in 60/120896 control chromosomes (2 homozygotes), predominantly observed in the South Asians, a frequency of 0.0036399 (60/16484). This subpopulation frequency is about 5 times the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503), suggesting this is likely a benign polymorphism found primarily in the populations of South Asian origin. The variant has been cited in 2 breast cancer patients without evidence of causality (i.e. co-segregation). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as Benign/Likely Benign. Taken together and based on the high allele frequency in the South Asian subpopulation in the ExAC database, this missense variant is classified as Benign.
3DMed Clinical Laboratory Inc RCV000677855 SCV000804015 uncertain significance Neoplasm of the breast 2017-06-24 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000587492 SCV000887749 benign not provided 2018-06-27 criteria provided, single submitter clinical testing
Color RCV000129740 SCV000910641 benign Hereditary cancer-predisposing syndrome 2016-06-14 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000082883 SCV000114957 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing

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