ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3305A>G (p.Asn1102Ser) (rs80356900)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000214206 SCV000274806 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-28 criteria provided, single submitter clinical testing The p.N1102S variant (also known as c.3305A>G), located in coding exon 9 of the BRCA1 gene, results from an A to G substitution at nucleotide position 3305. The asparagine at codon 1102 is replaced by serine, an amino acid with highly similar properties. This alteration was reported with a minor allele frequency of 0.30% in a Croatian cohort of 167 patients with a personal and/or family history of breast and/or ovarian cancer (Levanat S et al. Gene 2012 May; 498(2):169-76). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000506903 SCV000600325 uncertain significance not specified 2017-06-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000506903 SCV001338189 uncertain significance not specified 2020-02-24 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3305A>G (p.Asn1102Ser) results in a conservative amino acid change in the encoded protein sequence. Five of five 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 250622 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3305A>G has been reported in the literature in studies involving individuals affected with Hereditary Breast and Ovarian Cancer (example, Judkins_2005, Caux-Moncoutier_2011, Levanat_2012). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Color Health, Inc RCV000214206 SCV001344321 likely benign Hereditary cancer-predisposing syndrome 2017-05-08 criteria provided, single submitter clinical testing
Invitae RCV001350762 SCV001545180 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-10-05 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 1102 of the BRCA1 protein (p.Asn1102Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs80356900, ExAC 0.001%). This variant has been reported in families with breast and/or ovarian cancer (PMID: 22366370, 21120943). ClinVar contains an entry for this variant (Variation ID: 54831). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Tolerated; PolyPhen-2: Benign; Align-GVGD: Class C0. The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Breast Cancer Information Core (BIC) (BRCA1) RCV000112054 SCV000144707 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.