ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5745G>A (p.Thr1915=) (rs1799953)

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Total submissions: 6
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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) RCV000495474 SCV000578797 likely benign Breast-ovarian cancer, familial 2 2017-06-29 reviewed by expert panel curation Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/).
Ambry Genetics RCV000163123 SCV000213635 likely benign Hereditary cancer-predisposing syndrome 2014-11-26 criteria provided, single submitter clinical testing
Invitae RCV000227831 SCV000283271 likely benign not provided 2019-03-01 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000501495 SCV000591996 likely benign not specified 2014-01-30 criteria provided, single submitter clinical testing
Color RCV000163123 SCV000688944 likely benign Hereditary cancer-predisposing syndrome 2017-06-12 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000501495 SCV000916898 likely benign not specified 2019-04-16 criteria provided, single submitter clinical testing Variant summary: BRCA2 c.5745G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2.4e-05 in 250576 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.5745G>A has been reported in the literature in affected individual(s) (Caux-Moncoutier_BRCA2_HM_2011). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. The variant has also been reported in the FLOSSIES database in a woman older than age 70 years who has never had cancer, providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submissions from clinical diagnostic laboratories and an expert panel (ENIGMA) (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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