ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.5453A>G (p.Asp1818Gly) (rs80357477)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215390 SCV000274108 likely pathogenic Hereditary cancer-predisposing syndrome 2017-09-27 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Functionally-validated splicing mutation,Rarity in general population databases (dbsnp, esp, 1000 genomes)
Breast Cancer Information Core (BIC) (BRCA1) RCV000031253 SCV000145518 uncertain significance Breast-ovarian cancer, familial 1 2003-12-23 no assertion criteria provided clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000257937 SCV000324810 uncertain significance Hereditary breast and ovarian cancer syndrome 2015-09-11 criteria provided, single submitter clinical testing
Color RCV000215390 SCV000905197 pathogenic Hereditary cancer-predisposing syndrome 2015-09-01 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031253 SCV000326317 pathogenic Breast-ovarian cancer, familial 1 2015-10-02 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000257937 SCV000699255 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-01-08 criteria provided, single submitter clinical testing Variant summary: Variant affects a non-conserved nucleotide predicted to result in a replacement of a medium size and acidic Aspartate (D) with a small size and hydrophobic Glycine (G). 2/3 in silico tools predict disease causing outcome for this substitution (SNPs&GO and Mutation taster were not considered due to low reliability index). The variant is absent from the large and broad cohorts of the ExAC project while it was reported in three HBOC families (Rouleau_CGC_2010) indicating the variant to be in the pathogenic spectrum. Additionally, Rouleau_CGC_2010 and Houdayer_BRCA1&2_HM_2012 studied the effect of the variant on splicing using LCLs derived from variant carrier patients demonstrated the variant to result in exon 23 skipping and a to generate a frameshift p.Gly1803GlnfsX11 BRCA1 protein further supporting the variant to be deleterious. Moreover, GeneDX and SCRP classify the variant as Pathogenic via ClinVar (without evidence to independently evaluate). Taken all together the variant was classified as a Likely Pathogenic.
Sharing Clinical Reports Project (SCRP) RCV000031253 SCV000053857 pathogenic Breast-ovarian cancer, familial 1 2010-12-09 no assertion criteria provided clinical testing

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