Submissions for variant NM_007294.4(BRCA1):c.5586C>T (p.His1862=)

gnomAD frequency: 0.00001  dbSNP: rs774127304

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000495784	SCV000578420	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/).
Ambry Genetics	RCV000164747	SCV000215421	likely benign	Hereditary cancer-predisposing syndrome	2014-06-09	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.
Invitae	RCV001080604	SCV000289832	likely benign	Hereditary breast ovarian cancer syndrome	2024-01-11	criteria provided, single submitter	clinical testing
GeneDx	RCV000233978	SCV000512324	likely benign	not provided	2019-04-01	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 10196379)
Color Diagnostics, LLC DBA Color Health	RCV000164747	SCV000911266	likely benign	Hereditary cancer-predisposing syndrome	2017-12-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000495784	SCV001284848	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000426944	SCV001338558	likely benign	not specified	2020-04-02	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000426944	SCV002070586	likely benign	not specified	2021-10-15	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000426944	SCV002550939	likely benign	not specified	2023-08-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003954974	SCV004773085	likely benign	BRCA1-related condition	2020-11-15	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).