ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.322A>C (p.Asn108His) (rs80358567)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131576 SCV000186584 uncertain significance Hereditary cancer-predisposing syndrome 2018-03-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Breast Cancer Information Core (BIC) (BRCA2) RCV000113415 SCV000146588 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Color RCV000131576 SCV000903028 likely benign Hereditary cancer-predisposing syndrome 2016-06-30 criteria provided, single submitter clinical testing
Counsyl RCV000113415 SCV000488864 uncertain significance Breast-ovarian cancer, familial 2 2016-07-07 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000590284 SCV000230001 uncertain significance not provided 2014-11-13 criteria provided, single submitter clinical testing
GeneDx RCV000590284 SCV000210232 uncertain significance not provided 2018-09-25 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.322A>C at the cDNA level, p.Asn108His (N108H) at the protein level, and results in the change of an Asparagine to a Histidine (AAT>CAT). Using alternate nomenclature, this variant has been previously published as BRCA2 550A>C. This variant has been observed in several individuals and families with breast and/or ovarian cancer, but has also been observed in healthy control individuals of African descent (Wagner 1999, Gao 2000, Diez 2003, Nanda 2005, Lu 2012, Moghadasi 2013). BRCA2 Asn108His was observed at an allele frequency of 0.13% (32/23998) in individuals of African ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In-silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether BRCA2 Asn108His is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000590284 SCV000694681 uncertain significance not provided 2016-04-18 criteria provided, single submitter clinical testing Variant summary:The c.322A>C variant affects a not conserved nucleotide, resulting in amino acid change from Asn to His. 4/5 in-silico tools predict this variant to be benign. This variant is found in 9/113860 control chromosomes at a frequency of 0.000079, which does not exceed maximal expected frequency of a pathogenic allele (0.0007503). The variant was only found in African population with an allele frequency of 0.00091 (9/9786 chromosomes) which is insignificantly greater (~1.22 times greater) than the maximal expected allele frequency. The finding may suggests that the variant might be a rare benign polymorphism in Africans however supporting data are lacking. The variant of interest has been detected in multiple HBOC patients/families but with limited information to co-occurrence and co-segregation. In addition, multiple reputable diagnostic laboratories/databases have classified the variant as "uncertain significance." Therefore, until additional information becomes available, the variant of interest is classified as a Variant of Uncertain Significance.
Invitae RCV000167803 SCV000072166 likely benign Hereditary breast and ovarian cancer syndrome 2018-01-04 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000168534 SCV000600542 uncertain significance not specified 2016-11-23 criteria provided, single submitter clinical testing

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