ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.516+14C>T (rs182828913)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000119227 SCV000153972 benign Hereditary breast and ovarian cancer syndrome 2020-12-04 criteria provided, single submitter clinical testing
GeneDx RCV000179248 SCV000167323 benign not specified 2014-01-27 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.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000179248 SCV000231468 benign not specified 2014-12-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000119227 SCV000494399 benign Hereditary breast and ovarian cancer syndrome 2016-06-20 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.516+14C>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing, which was confirmed by multiple functional studies (Bonnet_2008, Houdayer_2012, Menendez_2012, de Garibay_2014). Although this variant has been reported in breast cancer patients, this variant was also found in 36/117190 control chromosomes, predominantly observed in the Latino subpopulation at a frequency of 0.0027521 (31/11264). This frequency is about 4 times the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. In addition, co-occurrences of this variant and a pathogenic BRCA1 variant have been reported in at least two patients (Garcia-Casado_2011 and UMD database). Furthermore, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. Taken together, this variant is classified as benign.
Baylor Genetics RCV000456351 SCV000541071 benign Familial cancer of breast 2017-02-23 criteria provided, single submitter clinical testing
Color Health, Inc RCV000581137 SCV000683678 benign Hereditary cancer-predisposing syndrome 2015-04-25 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679175 SCV000805715 likely benign not provided 2016-12-30 criteria provided, single submitter clinical testing
Mendelics RCV000988987 SCV001138967 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 RCV000179248 SCV000591688 benign not specified no assertion criteria provided clinical testing The BRCA2 c.516+14C>T variant has been shown not to impact mRNA splicing in in vitro splicing assays (Bonnet 2008, Houdayer2012). The variant was identified in dbSNP (ID: rs rs182828913) “With benign allele”, with a minor allele frequency of .0006/3 (1000 Genomes Project, in 3 of 5000 chromosomes, frequency 0.0006), the Exome Aggregation Consortium (ExAC) database (released Oct 20th, 2014) in 36 of 116930 chromosomes (frequency: 0.0003) (or 5 individuals from a population of 63686 European (Non-Finnish) individuals, 31 of 11264 Latino individuals, and none from East Asian, Other, African, South Asian or European (Finnish) individuals; Clinvitae database (2X as benign/likely benign), the ClinVar database (classified as a benign variant by Invitae and GeneDX), GeneInsight COGR database (1X, unclassified by a clinical laboratory), and UMD (12X as a likely neutral variant, with a co-occurring pathogenic BRCA1 variant (c.-200_80del (p.Met1SerfsX13)), increasing the likelihood that the c.516+14C>T variant does not have clinical significance. The variant was also identified by our laboratory in 1 individual with breast cancer. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000679175 SCV001927954 likely benign not provided no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000679175 SCV001955515 likely benign not provided no assertion criteria provided clinical testing

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