ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.506A>G (p.Lys169Arg) (rs80358730)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044547 SCV000072560 benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
GeneDx RCV000074532 SCV000108617 likely benign not specified 2017-11-06 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.
Ambry Genetics RCV000129126 SCV000183844 likely benign Hereditary cancer-predisposing syndrome 2018-09-06 criteria provided, single submitter clinical testing In silico models in agreement (benign);Other data supporting benign classification
Michigan Medical Genetics Laboratories,University of Michigan RCV000031522 SCV000267730 likely benign Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Counsyl RCV000031522 SCV000487798 uncertain significance Breast-ovarian cancer, familial 2 2015-11-17 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000074532 SCV000591687 uncertain significance not specified 2015-01-19 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001281705 SCV000600623 uncertain significance not provided 2020-03-13 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129126 SCV000910662 likely benign Hereditary cancer-predisposing syndrome 2015-11-16 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000031522 SCV001266518 uncertain significance Breast-ovarian cancer, familial 2 2017-04-28 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Clinical Services Laboratory,Illumina RCV001111540 SCV001269104 uncertain significance Fanconi anemia, complementation group D1 2017-04-28 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Integrated Genetics/Laboratory Corporation of America RCV000074532 SCV001361906 likely benign not specified 2019-03-13 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.506A>G (p.Lys169Arg) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 6.1e-05 in 246020 control chromosomes, predominantly at a frequency of 0.00013 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (6.1e-05 vs 0.00075), allowing no conclusion about variant significance. c.506A>G has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Davies_2018, Kote-Jarai_2011). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Co-occurrences with other pathogenic variants have been reported (BRCA2 c.8537_8538delAG (p.Glu2846Glyfs), BRCA1 c.188T>A (p.Leu63X) in the BIC database), providing supporting evidence for a benign role. A functional study, Houdayer_2012, found the variant to not have an impact on splicing. Seven ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant four times as likely benign/benign and three times as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign.
Sharing Clinical Reports Project (SCRP) RCV000031522 SCV000054127 benign Breast-ovarian cancer, familial 2 2007-04-03 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031522 SCV000147027 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing

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