Submissions for variant NM_000059.4(BRCA2):c.502C>A (p.Pro168Thr)

gnomAD frequency: 0.00014  dbSNP: rs80358726

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113704	SCV000244453	benign	Breast-ovarian cancer, familial, susceptibility to, 2	2015-08-10	reviewed by expert panel	curation	IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.0000316
Labcorp Genetics (formerly Invitae), Labcorp	RCV001080689	SCV000072553	benign	Hereditary breast ovarian cancer syndrome	2024-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000044540	SCV000210545	likely benign	not specified	2017-10-31	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	RCV000162997	SCV000213485	benign	Hereditary cancer-predisposing syndrome	2014-11-10	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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.
Eurofins Ntd Llc (ga)	RCV000590810	SCV000231467	uncertain significance	not provided	2014-08-22	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000162997	SCV000683666	likely benign	Hereditary cancer-predisposing syndrome	2016-03-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590810	SCV000694821	benign	not provided	2016-04-22	criteria provided, single submitter	clinical testing	Variant summary: The c.502C>A is a missense variant involves a conserved nucleotide and 5/5 in silico tools predict deleterious outcome. The variant is present in the control population dataset of ExAC at a frequency of 0.00084%, which does not exceed the maximal expected allele frequency for a non-common pathogenic BRCA2 variant (0.075%). The fact, that this variant co-occurred with different deleterious mutations in both BRCA1 and BRCA2 genes, suggest a non-disease causing nature of this variant. Diagnostics centers and several published reports classified this variant as Likely Benign and Benign. Taken all together, the variant was classified as Benign.
Mendelics	RCV000113704	SCV001138966	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2019-05-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000590810	SCV002506130	likely benign	not provided	2022-02-01	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113704	SCV000147017	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2002-05-29	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004528245	SCV000805714	likely benign	BRCA2-related disorder	2019-03-28	no assertion criteria provided	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).