Submissions for variant NM_007294.4(BRCA1):c.2352G>A (p.Ser784=)

gnomAD frequency: 0.00009  dbSNP: rs372017932

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000169468	SCV000578267	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2017-06-29	reviewed by expert panel	curation	Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
GeneDx	RCV000123905	SCV000167255	benign	not specified	2014-05-24	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics	RCV000163134	SCV000213648	likely benign	Hereditary cancer-predisposing syndrome	2014-10-08	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Counsyl	RCV000169468	SCV000220907	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2014-11-24	criteria provided, single submitter	literature only
Invitae	RCV000206665	SCV000260817	likely benign	Hereditary breast ovarian cancer syndrome	2024-01-29	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163134	SCV000537456	likely benign	Hereditary cancer-predisposing syndrome	2015-07-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000123905	SCV000916753	likely benign	not specified	2019-07-04	criteria provided, single submitter	clinical testing
Mendelics	RCV000169468	SCV001140574	likely benign	Breast-ovarian cancer, familial, susceptibility to, 1	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000169468	SCV001283969	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2017-04-28	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001354001	SCV002049107	likely benign	not provided	2021-04-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001354001	SCV002498279	likely benign	not provided	2022-10-01	criteria provided, single submitter	clinical testing	BRCA1: BP4, BP7
Sema4, Sema4	RCV000163134	SCV002538112	likely benign	Hereditary cancer-predisposing syndrome	2021-02-21	criteria provided, single submitter	curation
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354001	SCV000591382	likely benign	not provided		no assertion criteria provided	clinical testing	The BRCA1 p.Ser784Ser variant does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. Co-occurrences with other pathogenic variant(s) have been reported (BRCA1 c.886_889delAGAA, p.Arg296*; BRCA1 c.3748G>T, p.Glu1250*), providing supporting evidence for a benign role (ClinVar, SCV000916753.1). The variant was identified in control databases in 8 of 128598 chromosomes (0 homozygous) at a frequency of 0.000039, and was observed at the highest frequency in the European (non-Finnish) population in 8 of 128598 chromosomes (freq: 0.00006221) (Genome Aggregation Database March 6, 2019, v2.1.1). In summary, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001354001	SCV001800447	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV001354001	SCV001905861	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001354001	SCV001953965	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001354001	SCV001964081	likely benign	not provided		no assertion criteria provided	clinical testing