ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5986G>A (p.Ala1996Thr) (rs80358833)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000195331 SCV000072826 benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000129689 SCV000184490 likely benign Hereditary cancer-predisposing syndrome 2018-04-19 criteria provided, single submitter clinical testing Other data supporting benign classification;Subpopulation frequency in support of benign classification
GeneDx RCV000044813 SCV000210377 likely benign not specified 2017-08-17 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.
Illumina Clinical Services Laboratory,Illumina RCV000077366 SCV000383729 likely benign Breast-ovarian cancer, familial 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000318984 SCV000383730 likely benign Fanconi anemia, complementation group D1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000044813 SCV000538488 uncertain significance 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: 3 B/LB, 2 VUS; 1 paper in HGMD
Color RCV000129689 SCV000910686 benign Hereditary cancer-predisposing syndrome 2016-03-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000859013 SCV001133845 benign not provided 2018-08-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000044813 SCV001372452 likely benign not specified 2020-06-26 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.5986G>A (p.Ala1996Thr) results in a non-conservative amino acid change located in the BRCA2 repeat (IPR002093) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00048 in 251738 control chromosomes, predominantly at a frequency of 0.0037 within the South Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 5-fold of the estimated maximal expected allele frequency for a pathogenic variant in BRCA2 causing Hereditary Breast And Ovarian Cancer Syndrome phenotype (0.00075), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. c.5986G>A has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (e.g. Chan_2018, Darooei_2017, Juwle_2012, Kanchi_2014, Levanat_2012, Santonocito_2020) but also, in healthy controls (e.g. Lai_2017, Wen_2018). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign (n=6) and as uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely benign.
Sharing Clinical Reports Project (SCRP) RCV000077366 SCV000109163 benign Breast-ovarian cancer, familial 2 2012-06-05 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077366 SCV000146746 uncertain significance Breast-ovarian cancer, familial 2 2001-02-16 no assertion criteria provided clinical testing

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