ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.2481A>C (p.Glu827Asp) (rs397508970)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000216311 SCV000275030 likely benign Hereditary cancer-predisposing syndrome 2018-09-11 criteria provided, single submitter clinical testing No disease association in small case-control study
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000590050 SCV000698960 uncertain significance not provided 2016-06-06 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.2481A>C (p.Glu827Asp) variant involves the alteration of a non-conserved nucleotide. 3/4 in silico tools predict a benign outcome (SNPs&GO not captured due to low reliability index). This variant was found in 4/121702 control chromosomes at a frequency of 0.0000329, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). This variant has been reported in BrC pts as well as in normal controls in literatures. In addition, one clinical diagnostic laboratory via ClinVar classified this variant as likely benign and another lab via ClinVar classified this variant as VUS, without evidence to independently evaluate. Because of the absence of clinical information and the lack of functional studies, the variant was classified as a variant of uncertain significance (VUS) until additional information becomes available.
Color Health, Inc RCV000216311 SCV000909343 uncertain significance Hereditary cancer-predisposing syndrome 2020-08-26 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with aspartic acid at codon 827 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with breast cancer, as well as in unaffected controls (PMID: 16949048, 17100994). This variant has been identified in 1/250944 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Invitae RCV001345360 SCV001539471 uncertain significance Hereditary breast and ovarian cancer syndrome 2020-03-18 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with aspartic acid at codon 827 of the BRCA1 protein (p.Glu827Asp). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. This variant is present in population databases (rs397508970, ExAC 0.01%). This variant has been reported in individuals affected with breast cancer or hereditary breast and ovarian cancer syndrome (PMID: 17100994, 27383479). ClinVar contains an entry for this variant (Variation ID: 54580). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but 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.
Sharing Clinical Reports Project (SCRP) RCV000077520 SCV000109321 uncertain significance Breast-ovarian cancer, familial 1 2009-03-25 no assertion criteria provided clinical testing

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