Submissions for variant NM_007294.4(BRCA1):c.548-9del

dbSNP: rs273902774

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000588280	SCV000209914	likely benign	not provided	2020-11-16	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22034289, 16267036)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080904	SCV000253518	benign	Hereditary breast ovarian cancer syndrome	2024-12-18	criteria provided, single submitter	clinical testing
Counsyl	RCV000031259	SCV000489382	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2016-09-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000159865	SCV000699265	likely benign	not specified	2025-02-12	criteria provided, single submitter	clinical testing	Variant summary: BRCA1 c.548-9delA alters a non-conserved nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.9e-05 in 273214 control chromosomes, predominantly at a frequency of 0.00038 within the African or African-American subpopulation in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.548-9delA has been reported in the literature in individuals affected with breast and/or ovarian cancer (example, Cheng_2017, Diaz-Zabala_2018, Judkins_2005, Fackenthal_2012). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 16267036, 22034289, 28526081, 30400234, 32467295, 38566028). ClinVar contains an entry for this variant (Variation ID: 37678). Based on the evidence outlined above, the variant was classified as likely benign.
Eurofins Ntd Llc (ga)	RCV000588280	SCV000702258	uncertain significance	not provided	2016-10-03	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000776096	SCV000910902	likely benign	Hereditary cancer-predisposing syndrome	2016-04-07	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000588280	SCV001469399	likely benign	not provided	2023-03-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000588280	SCV001472546	likely benign	not provided	2019-12-12	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000776096	SCV002537864	likely benign	Hereditary cancer-predisposing syndrome	2022-01-22	criteria provided, single submitter	curation
Sharing Clinical Reports Project (SCRP)	RCV000031259	SCV000053863	benign	Breast-ovarian cancer, familial, susceptibility to, 1	2009-11-04	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000031259	SCV000145626	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2002-06-20	no assertion criteria provided	clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000735565	SCV000863703	benign	Breast and/or ovarian cancer		no assertion criteria provided	clinical testing