ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3071G>A (p.Ser1024Asn) (rs757579891)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167469 SCV000218325 uncertain significance Hereditary cancer-predisposing syndrome 2017-03-16 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;In silico models in agreement (benign)
Invitae RCV000695024 SCV000823498 uncertain significance Hereditary breast and ovarian cancer syndrome 2019-12-31 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 1024 of the BRCA1 protein (p.Ser1024Asn). The serine residue is moderately conserved and there is a small physicochemical difference between serine and asparagine. This variant is present in population databases (rs757579891, ExAC 0.01%). This variant has been reported in individuals in the Leiden Open-source Variation Database (PMID: 21520333). ClinVar contains an entry for this variant (Variation ID: 187719). 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 asparagine 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.
Color RCV000167469 SCV001354375 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-01 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001251419 SCV001427009 uncertain significance not specified 2020-07-30 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.3071G>A (p.Ser1024Asn) 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 4e-06 in 251078 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3071G>A in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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