Submissions for variant NM_007294.4(BRCA1):c.951A>G (p.Gln317=)

dbSNP: rs759419385

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000495807	SCV000578374	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/).
Invitae	RCV000206010	SCV000259964	likely benign	Hereditary breast ovarian cancer syndrome	2023-11-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000571430	SCV000664933	likely benign	Hereditary cancer-predisposing syndrome	2016-01-08	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.
Color Diagnostics, LLC DBA Color Health	RCV000571430	SCV000683378	likely benign	Hereditary cancer-predisposing syndrome	2017-01-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000615205	SCV000728007	likely benign	not specified	2018-02-22	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.
PreventionGenetics, part of Exact Sciences	RCV000679705	SCV000806987	likely benign	not provided	2017-12-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000615205	SCV000916742	likely benign	not specified	2018-05-25	criteria provided, single submitter	clinical testing	Variant summary: BRCA1 c.951A>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational 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 8.2e-06 in 121408 control chromosomes, predominantly at a frequency of 1.5e-05 within the Non-Finnish European subpopulation in the ExAC database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.951A>G has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. These report(s) cite the variant as unlikely to be associated with Hereditary Breast and Ovarian Cancer (Judkins_2005). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.