ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.8421G>A (p.Ser2807=) (rs371278843)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000409819 SCV000578018 benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/) and frequency 0.0028 (South Asian), derived from ExAC (2014-12-17).
GeneDx RCV000160251 SCV000210669 benign not specified 2014-10-03 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 RCV000163212 SCV000213735 likely benign Hereditary cancer-predisposing syndrome 2014-11-06 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 RCV001085334 SCV000252615 benign Hereditary breast and ovarian cancer syndrome 2020-12-06 criteria provided, single submitter clinical testing
Counsyl RCV000409819 SCV000488659 likely benign Breast-ovarian cancer, familial 2 2016-05-18 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163212 SCV000683966 likely benign Hereditary cancer-predisposing syndrome 2015-10-16 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000758961 SCV000887941 benign not provided 2019-03-22 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000160251 SCV001158087 benign not specified 2018-12-31 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353520 SCV000592190 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Ser2807Ser variant was not identified in the literature. The variant was identified in dbSNP (ID: rs371278843) “With Likely benign allele”, NHLBI Exome Sequencing Project (Exome Variant Server), Exome Aggregation Consortium (ExAC) database, the ClinVar database (classified as a benign variant by GeneDx; classified as likely benign by Ambry Genetics), GeneInsight COGR database (1X, classified as “likely benign” by a clinical laboratory), and UMD (1X as a UV variant). This variant was identified in the Exome Variant Server project in 1 of 4406 African American alleles, the Exome Aggregation Consortium (ExAC) database (released Jan 13, 2015). The variant was also identified in 46 of 16508 individuals from South Asia (frequency: 0.0028) and once in homozygous state, increasing the likelihood this variant does not have clinical significance. It was also identified in one East Asian and one African individual, increasing the likelihood this could be a low frequency benign variant in certain populations of origin. The p.Ser2807Ser variant 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. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. It should be noted that another variant at the same position (c.8421G>T, p.Ser2807Ser) did not show splicing aberration and classified as Class 2, likely not pathogenic, according to the IARC 5 class system (Thomassen 2012). In summary, based on the above information this variant is classified as benign.
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000758961 SCV001906060 likely benign not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000758961 SCV001953442 likely benign not provided no assertion criteria provided clinical testing

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