ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5152+5G>A (rs80358165)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000083217 SCV000326178 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779869 SCV000916740 pathogenic Hereditary breast and ovarian cancer syndrome 2018-03-26 criteria provided, single submitter clinical testing Variant summary: BRCA1 c.5152+5G>A alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site and one predict a significant weaking effect on the 5' donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing, with skipping of exon 18 (Campos_2003). The variant was absent in 246244 control chromosomes (gnomAD). c.5152+5G>A has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer (Jimenez_2013, Diez_2003, Shi_2017, Campos_2003). These data indicate that the variant is very likely to be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Color Health, Inc RCV001179280 SCV001343896 likely pathogenic Hereditary cancer-predisposing syndrome 2020-01-28 criteria provided, single submitter clinical testing
Invitae RCV000779869 SCV001582574 pathogenic Hereditary breast and ovarian cancer syndrome 2020-01-23 criteria provided, single submitter clinical testing This sequence change falls in intron 17 of the BRCA1 gene. It does not directly change the encoded amino acid sequence of the BRCA1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals and families affected with breast and/or ovarian cancer (PMID: 12955716, 12955719, 29470806, 23479189). This variant is also known as 5271+5G>A and IVS18+5G>A in the literature. ClinVar contains an entry for this variant (Variation ID: 55427). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing and BRCA1 protein function (PMID: 12955719, 30209399). For these reasons, this variant has been classified as Pathogenic.
Research and Development, ARUP Laboratories RCV001664026 SCV001877454 pathogenic Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2021-05-01 criteria provided, single submitter curation
Sharing Clinical Reports Project (SCRP) RCV000083217 SCV000115291 likely pathogenic Breast-ovarian cancer, familial 1 2012-11-21 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000083217 SCV000145341 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Brotman Baty Institute,University of Washington RCV000083217 SCV001242221 not provided Breast-ovarian cancer, familial 1 no assertion provided in vitro

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