ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1909+9_1909+10del (rs527732001)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000168553 SCV000210573 benign not specified 2014-07-02 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 RCV000168553 SCV000224762 likely benign not specified 2014-11-04 criteria provided, single submitter clinical testing
Invitae RCV000205851 SCV000261658 benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000205851 SCV000383642 likely benign Hereditary breast and ovarian cancer syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000263361 SCV000383643 likely benign Fanconi anemia 2016-06-14 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000168553 SCV000593705 likely benign not specified 2017-04-07 criteria provided, single submitter clinical testing
Color Health, Inc RCV000580167 SCV000683459 benign Hereditary cancer-predisposing syndrome 2015-09-30 criteria provided, single submitter clinical testing
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital RCV000205851 SCV000891008 likely benign Hereditary breast and ovarian cancer syndrome 2020-12-03 criteria provided, single submitter clinical testing The BRCA2 c.1909+9_1909+10delGT intronic deletion has a maximum subpopulation frequency of 0.51% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/variant/13-32907531-CTG-C). This frequency is higher than would be expected for a pathogenic variant in BRCA2 (BS1; PMID: 28166811). In silico predictors are in agreement that this variant does not affect splicing (BP4). In summary, this variant meets criteria to be classified as likely benign based on the ACMG/AMP criteria: BS1, BP4.
Mendelics RCV000989004 SCV001139013 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283319 SCV001160594 benign none provided 2020-01-31 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001270287 SCV000591781 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 c.1909+9_1909+10delGT variant was not identified in the literature nor was it identified in the COSMIC database. The variant was identified in dbSNP (rs527732001). The c.1909+9_1909+10delGT variant was identified (2x as unknown variant) in UMD database and co-occurred with 2 unknown variants on both occasions i.e. c.1798T>C (p.Tyr600His) and c.7504C>T (p.Arg2502Cys). The variant was identified in control databases in 127 of 266616 chromosomes at a frequency of 0.0004763 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: African in 119 of 23226 chromosomes (freq: 0.005124), Latino in 6 of 34390 chromosomes (freq: 0.000175), European (non-Finnish) in 2 of 120976 chromosomes (freq: 0.000017), but was not observed in the Ashkenazi Jewish, East Asian, European (Finnish), Other, or South Asian populations. The variant was identified in ClinVar (benign 4x, likely benign 5x, VUS 1x) and LOVD 3.0 (3 entries, VUS 2x, benign 1x) databases. The c.1909+9_1909+10delGT variant occurs outside of the splicing consensus sequence and five in silico or computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. However, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time, thought we would lean toward a more benign role for this variant. This variant is classified as likely benign.
True Health Diagnostics RCV000580167 SCV000787921 likely benign Hereditary cancer-predisposing syndrome 2018-01-05 no assertion criteria provided clinical testing

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