ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.1609A>G (p.Asn537Asp)

gnomAD frequency: 0.00001  dbSNP: rs398122639
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131971 SCV000187029 likely benign Hereditary cancer-predisposing syndrome 2019-02-26 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Invitae RCV001087842 SCV000289748 likely benign Hereditary breast ovarian cancer syndrome 2024-01-03 criteria provided, single submitter clinical testing
GeneDx RCV000605647 SCV000729886 likely benign not specified 2017-11-09 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 RCV000077075 SCV000785431 uncertain significance Breast-ovarian cancer, familial, susceptibility to, 1 2017-08-04 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000131971 SCV000909373 likely benign Hereditary cancer-predisposing syndrome 2017-11-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000605647 SCV000918681 uncertain significance not specified 2023-10-13 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.1609A>G (p.Asn537Asp) results in a conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250852 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1609A>G has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (e.g. Borg_2010, Capanu_2011, Hercules_2022). 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. The following publications have been ascertained in the context of this evaluation (PMID: 20104584, 21520273, 35384527, 30212499). Eight submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Multiple submitters reported the variant with conflicting assessments (likely benign, n=5; uncertain significance, n=3). Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000232941 SCV001133492 uncertain significance not provided 2019-05-09 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000131971 SCV002538042 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-29 criteria provided, single submitter curation
University of Washington Department of Laboratory Medicine, University of Washington RCV000131971 SCV003851175 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Sharing Clinical Reports Project (SCRP) RCV000077075 SCV000108872 benign Breast-ovarian cancer, familial, susceptibility to, 1 2008-11-11 no assertion criteria provided clinical testing

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