Submissions for variant NM_007294.4(BRCA1):c.5453A>G (p.Asp1818Gly) (rs80357477)

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000215390	SCV000274108	likely pathogenic	Hereditary cancer-predisposing syndrome	2018-12-24	criteria provided, single submitter	clinical testing	Rarity in general population databases (dbsnp, esp, 1000 genomes);Other strong data supporting pathogenic classification;Deficient protein function in appropriate functional assay(s)
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario	RCV001095362	SCV000324810	likely pathogenic	Breast and/or ovarian cancer	2018-03-29	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.
Color	RCV000215390	SCV000905197	pathogenic	Hereditary cancer-predisposing syndrome	2015-09-01	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000031253	SCV000053857	pathogenic	Breast-ovarian cancer, familial 1	2010-12-09	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000031253	SCV000145518	uncertain significance	Breast-ovarian cancer, familial 1	2003-12-23	no assertion criteria provided	clinical testing
Brotman Baty Institute,University of Washington	RCV000031253	SCV001243349	not provided	Breast-ovarian cancer, familial 1		no assertion provided	in vitro