Submissions for variant NM_007294.4(BRCA1):c.-86C>T

gnomAD frequency: 0.00077  dbSNP: rs143160357

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000354064	SCV000403079	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genetic Services Laboratory, University of Chicago	RCV000501570	SCV000593668	benign	not specified	2021-06-14	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001690071	SCV002498283	benign	not provided	2025-02-01	criteria provided, single submitter	clinical testing	BRCA1: BS1, BS2
Labcorp Genetics (formerly Invitae), Labcorp	RCV003105869	SCV003780258	benign	Hereditary breast ovarian cancer syndrome	2023-01-08	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000501570	SCV000591223	benign	not specified		no assertion criteria provided	clinical testing	#N/A
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research	RCV000735614	SCV000863752	benign	Breast and/or ovarian cancer	2013-06-18	no assertion criteria provided	clinical testing
Center of Medical Genetics and Primary Health Care	RCV001004838	SCV000987262	uncertain significance	Malignant tumor of breast	2020-04-08	no assertion criteria provided	research	ACMG Guidelines 2015 criteria This variant is in the 5' UTR of the BRCA1 gene. This variant has been reported in a few cases in ClinVar as a VUS. 1 benign prediction from DANN versus no pathogenic predictions supports its benign effect (BP4 Benign Supporting). In our study it was detected in a 30-year-old female patient with unilateral breast cancer and no reported family history of cancer. Therefore, due to lack of sufficient evidence we classified this variant as a Variant of Uncertain Significance.
Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	RCV001690071	SCV001906255	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001690071	SCV001956139	likely benign	not provided		no assertion criteria provided	clinical testing