ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.2771A>T (p.Asn924Ile) (rs80358530)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001079700 SCV000072065 benign Hereditary breast and ovarian cancer syndrome 2020-12-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000130266 SCV000185110 uncertain significance Hereditary cancer-predisposing syndrome 2020-09-22 criteria provided, single submitter clinical testing The p.N924I variant (also known as c.2771A>T), located in coding exon 10 of the BRCA2 gene, results from an A to T substitution at nucleotide position 2771. The asparagine at codon 924 is replaced by isoleucine, an amino acid with dissimilar properties. This variant has been described in a Spanish patient with early-onset breast cancer, whose family history included a grandmother diagnosed with leukemia at 35 years (de Sanjosé S et al. Int. J. Cancer. 2003 Sep;106:588-93). This alteration was also identified in 1/1358 non-cancer control individuals and in 0/57 cases, in a study looking at cancer predisposition mutations in patients with cutaneous melanoma and a history of at least two additional non-cutaneous melanoma primary cancers (Pritchard AL et al. PLoS ONE, 2018 Apr;13:e0194098). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000585963 SCV000694624 uncertain significance not provided 2017-06-29 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.2771A>T (p.Asn924Ile) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a damaging outcome for this variant. This variant was found in 2/120770 control chromosomes at a frequency of 0.0000166, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503). The variant has been reported in affected individuals in the literature, without strong evidence for causality. The variant has been reported to co-occur with two pathogenic BRCA1 mutations: AJ founder mutation BRCA1 c.68_69delAG (p.Glu23ValfsX17) from UMD and an exon 8-11 deletion from an internal LCA sample. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as has been classified as a VUS-possibly benign until additional clinical and functional data becomes available.
Color Health, Inc RCV000130266 SCV000911451 likely benign Hereditary cancer-predisposing syndrome 2018-01-30 criteria provided, single submitter clinical testing
Mendelics RCV000113089 SCV001139041 benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
GeneDx RCV000585963 SCV001793582 uncertain significance not provided 2019-09-27 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Observed in individuals with breast cancer (de Sanjose 2003, Velasco 2005, Wong-Brown 2015); This variant is associated with the following publications: (PMID: 30212499, 15937982, 25682074, 23929434, 12845657)
Breast Cancer Information Core (BIC) (BRCA2) RCV000113089 SCV000146105 uncertain significance Breast-ovarian cancer, familial 2 2004-02-20 no assertion criteria provided clinical testing
Sharing Clinical Reports Project (SCRP) RCV000113089 SCV000297515 likely benign Breast-ovarian cancer, familial 2 2011-02-18 no assertion criteria provided clinical testing

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