Submissions for variant NM_000059.4(BRCA2):c.7506C>T (p.Arg2502=)

dbSNP: rs140693106

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)	RCV000411370	SCV000579048	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	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	RCV000168603	SCV000210653	benign	not specified	2014-07-16	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	RCV000165575	SCV000216309	likely benign	Hereditary cancer-predisposing syndrome	2014-08-20	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	RCV000198623	SCV000253036	likely benign	Hereditary breast ovarian cancer syndrome	2024-01-22	criteria provided, single submitter	clinical testing
Counsyl	RCV000411370	SCV000488649	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2016-05-18	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000165575	SCV001344652	likely benign	Hereditary cancer-predisposing syndrome	2017-01-22	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001284439	SCV001470239	likely benign	not provided	2019-12-23	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000165575	SCV002531864	likely benign	Hereditary cancer-predisposing syndrome	2021-11-15	criteria provided, single submitter	curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000168603	SCV002570802	likely benign	not specified	2022-07-11	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000411370	SCV000592117	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2		no assertion criteria provided	clinical testing	The p.Arg2502Arg is not expected to have clinical significance because it 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, HumanSpliceFinder) do not predict a difference in splicing. The variant was not identified in the literature nor was it identified in HGMD, LOVD, COSMIC, UMD, ClinVar, or BIC databases. It was identified in the NHLBI Exome Sequencing Project (Exome Variant Server) with an allele frequency 1/4406 in African American population. It is listed in the dbSNP database (rs140693106) but no frequency information was provided, thus the prevalence of this variant in the general population could not be determined. The IARC database shows that any substitution at nucleotide position 7506 results in the formation of the same Arg residue at this codon 2502. In summary, based on the above information, 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 predicted benign.