ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.179A>G (p.Asn60Ser) (rs80358463)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001082266 SCV000071903 likely benign Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130469 SCV000185335 likely benign Hereditary cancer-predisposing syndrome 2018-11-06 criteria provided, single submitter clinical testing Other data supporting benign classification;In silico models in agreement (benign)
GeneDx RCV000168530 SCV000210660 likely benign not specified 2017-12-13 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.
Counsyl RCV000031339 SCV000487989 uncertain significance Breast-ovarian cancer, familial 2 2015-12-13 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000168530 SCV000694566 benign not specified 2019-12-26 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.179A>G (p.Asn60Ser) 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 2.4e-05 in 251386 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.179A>G has been reported in the literature in sequencing studies of individuals affected with Breast Cancer (example, Muller_2011, Borg_2010, Capanu_2011, Claes_2004, Baeyens_2004). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Furthermore, at-least two reports of its occurrence among women who are cancer free and older than 70 has been observed (FLOSSIES database). At-least three co-occurrences with other pathogenic variant(s) have been reported in external databases as well as our laboratory (BRCA1 c.3949_3976dup, p.His1326LeufsX13 in UMD database; BRCA1 c.2767_2770delGTTA, p.Val923_Asn924?fs in BIC database; BRCA1 c.181T>C, p.Cys61Gly at our laboratory), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Four out of these five submitters classified the variant as benign (n=1)/likely benign (n=4), while one has classified it as a VUS. Most laboratories utilize overlapping publications utilized in the context of this evaluation. Due to its inherent rarity, our laboratory has tracked this variant for 6 years reporting a classification of VUS-possibly benign. No strong evidence supporting a pathogenic outcome has been reported in this time frame and increasingly, all evidences seem to point towards a benign outcome. Based on the evidence outlined above, the variant was re-classified as benign.
Color RCV000130469 SCV000902888 benign Hereditary cancer-predisposing syndrome 2016-04-25 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000031339 SCV001272758 uncertain significance Breast-ovarian cancer, familial 2 2018-01-12 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 RCV001114847 SCV001272759 uncertain significance Fanconi anemia, complementation group D1 2018-01-12 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.
Sharing Clinical Reports Project (SCRP) RCV000031339 SCV000053944 benign Breast-ovarian cancer, familial 2 2009-01-22 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031339 SCV000146309 uncertain significance Breast-ovarian cancer, familial 2 1999-04-12 no assertion criteria provided clinical testing

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