ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.6057C>T (p.Asn2019=) (rs147961615)

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Total submissions: 14
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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) RCV000210964 SCV000578004 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 0.0061 (African), derived from ExAC (2014-12-17).
GeneDx RCV000123981 SCV000167376 benign not specified 2013-10-29 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.
Michigan Medical Genetics Laboratories,University of Michigan RCV000210964 SCV000195995 benign Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV000163115 SCV000213626 likely benign Hereditary cancer-predisposing syndrome 2014-07-01 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 RCV001079310 SCV000252609 benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
Color Health, Inc RCV000163115 SCV000683750 likely benign Hereditary cancer-predisposing syndrome 2015-04-08 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679179 SCV000805733 likely benign not provided 2017-07-11 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000123981 SCV000859228 benign not specified 2018-01-16 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000679179 SCV000885101 benign not provided 2017-07-17 criteria provided, single submitter clinical testing
Mendelics RCV000210964 SCV001139134 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353589 SCV000592023 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Asn2019Asn variant was identified in 9 of 868 proband chromosomes (frequency: 0.01) from individuals or families with breast cancer (Fackenthal 2012). The variant was also identified in dbSNP (ID: rs147961615) as “With Likely benign allele”, Clinvitae database (classified as benign by ClinVar and Invitae; classified as likely benign by ClinVar), the ClinVar database (classified as benign by GeneDx, Invitae, MMGLUM; classified as likely benign by Ambry genetics) and UMD (28x with an “unclassified variant” classification). In UMD the variant was identified with a co-occurring pathogenic BRCA2 variant (c.1310_1313delAAGA, p.Lys437IlefsX22), increasing the likelihood that the p.Asn2019Asn variant does not have clinical significance. This variant was identified in the 1000 Genomes Project in 12 of 5000 chromosomes (frequency: 0.002), the NHLBI GO Exome Sequencing Project in 19 of 4406 African American alleles, and the Exome Aggregation Consortium database (August 8, 2016) in 60 of 120608 chromosomes (freq. 0.0005) in the following populations: African in 59 of 10044 chromosomes (freq. 0.006) and Latino in 1 of 11568 chromosomes (freq. 0.00008), increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. The p.Asn2019Asn 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 3 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing. However, this information is not predictive enough to assume pathogenicity. 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 likely benign.
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000679179 SCV001905993 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000679179 SCV001930281 likely benign not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000123981 SCV001958661 benign not specified no assertion criteria provided clinical testing

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